JAMA: Early onset AF linked with death for women
Healthy women with a new-onset of atrial fibrillation (AF) saw a heightened risk of mortality and cardiovascular (CV) events, Swedish researchers found in a study published in the May 25 issue of the Journal of American Medical Association. However, an accompanying editorial questioned whether these women were actually as "healthy" as the researchers suggested.

Because little is known about the incident of AF and mortality in healthy middle-aged women, David Conen, MD, of the University Hospital in Basel, Switzerland, and colleagues examined the data of 34,722 women who were participating in the Women’s Health Study (WHS) between 1993 and March 16, 2010, to assess the influence of associated CV comorbidities on risk.

All-cause, cardiovascular and noncardiovascular mortality was used as the study’s primary endpoint.

During the study, 1,011 women developed a new-onset of AF and 64.9 percent of these patients were classified with paroxysmal AF. Of the women with a new onset of AF, 72.4 percent had hypertension, but were at a low risk of experiencing a bleeding event.

Most participants, 69.8 percent, had a CHADS2 score of one or lower. At the time of AF onset, 53 percent of patients were prescribed warfarin, 50 percent beta-blockers and 23 percent were administered calcium-channel blockers.

Patients with paroxysmal AF were younger and had a lower body mass index and a lower prevalence of hypertension compared with women with either persistent or chronic AF.

The researchers reported 63 deaths in women with an incident AF diagnosis and four of these deaths occurred within 30 days of AF onset; all were related to cardiovascular causes. After adjusting for CV risk factors the authors reported that 2.1 percent of the deaths could be attributed to incident AF. Patients with paroxysmal AF also had a higher risk of CV death but not all-cause death or death from noncardiovascular causes.

“Our study suggests that the risk of death is increased even in AF populations with a low burden of comorbidities and a low short-term mortality rate,” the authors wrote. However, the overall mortality rate was low, with only 2.1 percent of deaths attributed to AF.

However, in the accompanying JAMA editorial, Yoko Miyasaka, MD, PhD, and Teresa S. M. Tsang, MD, of the Kansai Medical University in Hirakata, Japan, and University of British Columbia in Vancouver, respectively, questioned whether these women could actually be classified as "healthy." While the population of women were free of cardiovascular disease at baseline, half the women who developed AF had hypertension and a third were diagnosed with hypercholesterolemia.

Additionally, women who had AF onset were more likely to have hypertension, diabetes, hypercholesterolemia, high body mass indexes and also smoke, Miyasaka and Tsang noted.

“This study adds to the prior literature by showing that adjustment for nonfatal cardiovascular events substantially attenuates the risk of death associated with AF, suggesting that this increased risk is partly mediated through the occurrence of nonfatal cardiovascular disease, particularly the development of CHF [congestive heart failure] and stroke,” Conen and colleagues noted.

While total and non-CV mortality was not increased in the population of women with paroxysmal AF, there was a heightened risk of cardiovascular mortality due to CV events. The researchers said these results should be interpreted with caution because of the low number of events among these women, the wide confidence intervals and the potential limited power of the trial.

Miyasaka and Tsang also noted that  “while it is important to link the finding of AF to death in a cohort of middle-aged women initially free of cardiovascular events, it is equally important to recognize that on a subclinical level, nearly half of the women who developed AF in the WHS cohort had an enlarged left atrium and a third had left ventricular hypertrophy, attesting to a high prevalence of subclinical structural substrates for AF.”

The editorial concluded that future studies should look to evaluate left atrial volume characterization, as left atrial enlargement has “been shown to be the common denominator for the pathophysiologic cascade that leads to AF, stroke independent of AF, heart failure and death.”

Conen et al speculated that some of the 63 deaths that occured within the study could have been preventable through drug therapy, including anticoagulation, or through optimal blood pressure control.  "What this means for women with atrial fibrillation is that it is very important to optimally manage risk factors for cardiovascular disease with the help of their physician,” Christine Albert, MD, senior author of the study and a cardiac electrophysiologist at Brigham and Women’s Hospital in Boston wrote. “However, there is also a portion of this increased risk that persists even when these cardiovascular conditions are taken into account. For this reason, more research is needed to further understand the causes of atrial fibrillation so that we might identify ways to prevent atrial fibrillation and death associated with it.”