New AF in Healthy Young Women Still Ups Death Rate

AF and death in healthy women

May 26, 2011

May 24, 2011 (Basel, Switzerland) - Healthy middle-aged women who develop atrial fibrillation (AF) still have an increased risk of death compared with similar women who do not have AF, according to new results covering 15 years of follow-up from the Women's Health Study (WHS) [1].

But the authors point out that a significant proportion of the excess mortality risk appears attributable to the occurrence of nonfatal cardiovascular events prior to death, and they suggest that there is thus an opportunity to improve the outcome of individuals with new-onset AF through both prevention and optimal management of these associated comorbidities.

"One of the take-home messages from this study is that cardiovascular risk factors should be managed aggressively in patients with AF to try to reduce these deaths. Once patients have developed a hard cardiovascular end point, the risk of mortality is much higher. We need strict control of weight and blood pressure before they develop such events," lead author Dr David Conen (University Hospital, Basel, Switzerland) commented to heartwire .

Conen explained that most previous studies looking at the risk of death in AF patients have involved elderly patients and those who already have cardiovascular disease. "The novel thing about the population in this study was that they were relatively healthy middle-aged women without cardiovascular disease at baseline. But still in this low-risk population, the development of AF was associated with an increase in mortality. We found that those who developed AF were twice as likely to die as those who didn't develop AF. Most of the deaths were cardiovascular. The cardiovascular death risk increased fourfold in AF vs non-AF patients, whereas the noncardiovascular deaths increased by about 60%. However, the absolute risk in our study was small, reflecting the low comorbidity burden."

The AF is causing strokes and heart failure, and these conditions are leading to the deaths.

He noted that in previous studies an increased risk of mortality has been seen in the short term after AF diagnosis, but this has been attributed to underlying comorbidities, as it is unlikely that new AF would increase mortality so quickly. "We didn't see this in the current study. We believe that this was because our population was healthy at the start--there was no burden of cardiovascular disease, so no short-term mortality risk. But still the mortality risk appeared to be driven by comorbidities that developed over the course of the study. If we adjust the results for nonfatal cardiovascular events such as stroke and heart failure, the risk of death substantially reduces. This suggests that the AF is causing strokes and heart failure, and these conditions are leading to the deaths. The AF is the starting point of the process."

For the current study, which is published in the May 25, 2011 issue of the Journal of the American Medical Association, the researchers analyzed results from 34 722 subjects aged between 49 and 59 participating in the Women's Health Study who were free of AF and cardiovascular disease at baseline.

During a median follow-up of 15.4 years, 1011 women developed AF. Those women who developed AF had an increased risk of all-cause, cardiovascular, and noncardiovascular mortality compared with women who did not develop AF.

Mortality rates per 1000 person-years for women who developed AF vs those who did not develop AF

Outcome AF No AF Adjusted hazard ratio (95% CI)
All-cause mortality 10.8 3.1 2.14 (1.64–2.77)
CV mortality 4.3 0.57 4.18 (2.69–6.51)
Non-CV mortality 6.5 2.5 1.66 (1.19–2.30)

Although the women in this study did not have cardiovascular disease at baseline, there was some hypertension and diabetes in the population. About 44% of the population had hypertension at enrollment, and 72% had hypertension at the time of AF development.

Lone AF--defined as AF in patients with no other comorbidities or risk factors--was not associated with increased risk of complications. None of 74 women with lone AF in this study died or had a stroke during a median follow-up of more than seven years, and only two developed heart failure.

The authors note that although this represents the largest prospective sample of women with lone AF reported so far, the number is still too small and follow-up is not long enough to draw definite conclusions about long-term outcomes. But they add that these data are consistent with prior observations that lone AF may be a benign disease, at least in the short term. Conen commented to heartwire : "It seems as though lone AF is just an electrical problem without any structural problem."

Aggressive detection and treatment necessary

In an accompanying editorial [2], Dr Yoko Miyasaka (Kansai Medical University, Hirakata, Japan, and Dr Teresa Tsang (University of British Columbia, Vancouver) say these latest results confirm that clinicians should be aggressive in detection and treatment of AF in apparently healthy individuals, as multiple studies have demonstrated that anticoagulation in AF patients reduces stroke risk and death.

However, noting that in the WHS cohort, nearly half of the women who subsequently developed AF had hypertension, a third had hypercholesterolemia, and 9% were current smokers at baseline, the editorialists question whether these women can be considered "healthy" even though they were event-free at baseline.

They further point out that while standardized echocardiographic studies were not performed in all women with incident AF in the study, structural abnormalities were common in the subgroup for whom echocardiographic data were available, with 41% having an enlarged left atrium at the time of AF diagnosis and 32% having left ventricular hypertrophy, suggesting that women who developed AF had preexisting structural substrates for this arrhythmia.

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