Atrial Fibrillation More Likely to Signal Heart Harm in Women Than Men

Marlene Busko

January 22, 2016

OXFORD, UK — Although previous smaller studies have reported conflicting findings about whether atrial fibrillation (AF) is more detrimental to health in women than in men, a new meta-analysis of 30 studies detected a definite gender difference[1].

Specifically, after adjustment for multiple confounders, AF was associated with a 12% greater risk of all-cause mortality in women compared with men in a 1- to 26-year follow-up. Strikingly, AF was also linked with an almost twofold higher risk of stroke and of cardiovascular mortality in women than in men.

The study by doctoral student Connor A Emdin (George Institute for Global Health, University of Oxford, UK) and colleagues was published online January 19, 2016 in the BMJ.

"By pooling together all available evidence, we were able to demonstrate that the negative findings" for increased risk from AF in women vs men in certain prior studies were likely due to "a lack of [statistical] power," Emdin told heartwire from Medscape. This meta-analysis also adds to the growing body of evidence showing that women have a disproportionate risk of adverse events from CVD risk factors such as smoking and diabetes, he noted.

The study has limitations that are inherent with observational studies and meta-analyses, and thus it cannot show cause and effect. But clinicians should be aware that this study showed that women with AF were at higher risk of cardiovascular complications than men, Emdin stressed. Thus, "it might be appropriate for clinicians to consider more aggressive treatment" of CV risk factors in women with AF, the researchers advise.

Impact of Irregular Heartbeat in Women vs Men

To determine whether AF is a stronger predictor of CVD and death in women than in men, Emdin and colleagues searched for studies published between 1966 and 2015 that had a minimum of 50 participants with AF and 50 participants without AF and that also reported sex-specific differences between AF and all-cause mortality, cardiovascular mortality, stroke, cardiac events (cardiac death and nonfatal MI), and heart failure.

They identified 30 studies with 4.37 million participants, of which 66,511 had AF. The participants had a mean age of 45 to 83 and were followed from 1 to 26 years. Each study adjusted the outcomes for age. Most also adjusted for multiple other CV risk factors, including hypertension, smoking, and diabetes

In a pooled analysis of the 30 studies, compared with other women, those with AF were four times more likely to have a stroke, after adjustment for multiple available confounders (relative risk [RR] 4.05; 95% CI 2.52–6.50).

Among men, compared with those without AF, those with AF were 1.8 times more likely to have a stroke (adjusted RR 1.77; 95% CI 1.40–2.24).

Having AF conferred a 1.99-fold higher risk of stroke in women compared with men, as well as significantly higher risks of the other studied CV and mortality outcomes in women compared with men.

Relative Risk of CVD and Death Conferred by AF, in Women vs Men

Outcome Adjusted Relative Risk (95% CI)
All-cause mortality 1.12 (1.07–1.17)
CVD mortality 1.93 (1.44–2.60)
Stroke 1.99 (1.46–2.71)
Cardiac events 1.55 (1.15–2.08)
Heart failure 1.16 (1.07–1.27)

"It is unclear what could cause the observed differences in risk of mortality and cardiovascular disease associated with AF between women and men," Emdin and colleagues acknowledge. Women with AF may be undertreated compared with men, or they may respond differently to oral anticoagulants, they suggest.

Thus, "future research should be encouraged to determine the underlying causes of the observed sex differences," they conclude.

Emdin is funded by Rhodes scholarships; disclosures for the coauthors are listed in the article.

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