A systematic review and meta-analysis of 30 cohort studies found that atrial fibrillation is associated with a stronger relative risk of cardiovascular disease and death in women compared with men.

However, the researchers indicated that further research was necessary to determine causality.

Lead researcher Connor A Emdin, DPhil, of the University of Oxford in the U.K., and colleagues published their results online in The BMJ on Jan. 19.

“Estimation of the global and regional burden of [atrial fibrillation] should be independent of sex,” they wrote. “Allocation of public health resources for prevention and treatment of [atrial fibrillation] should also consider the differential effects of [atrial fibrillation] by sex. Future research should be encouraged to determine the underlying causes of the observed sex differences.”

In 2010, an estimated 33.5 million people in the world had atrial fibrillation, which was associated with an age adjusted mortality rate of 1.7 per 100,000 people. The researchers noted that the prevalence of atrial fibrillation was increasing in developed and developing countries.

For this analysis, the researchers identified cohort studies that were published between 1966 and March 2015 and had a minimum of 50 participants
 with atrial fibrillation and 50 without, along with a median follow-up period of at least six months. The studies were required to report sex-specific associations between atrial fibrillation and any of the following outcomes: all cause mortality, cardiovascular mortality, stroke (fatal and nonfatal), cardiac events (a composite of cardiac death and nonfatal MI excluding heart failure), heart failure, peripheral arterial disease and chronic kidney disease in men and women.

Of the 30 cohort studies that met the inclusion criteria, 20 provided published sex specific associations and 10 provided unpublished associations. None of the studies reported sex specific associations for peripheral arterial disease or chronic kidney disease.

The studies included more than 4.3 million participants, including 66,511 with atrial fibrillation. In addition, 26 studies reported the number of events, including 14 with all cause mortality, four with cardiovascular mortality, 11 with stroke, six with cardiac events and three with heart failure.

The pooled relative risk of all cause mortality for participants with atrial fibrillation compared with those without atrial fibrillation was higher in women than in men. There was also a 12 percent greater risk of all cause mortality associated with AF in women than in men, according to the pooled ratio of relative risks.

The relative risk of stroke was also greater in women compared with men. The researchers found that atrial fibrillation was associated with twice the relative risk of stroke in women versus men.

In addition, atrial fibrillation was associated with a higher relative risk of cardiovascular mortality in women than in men and a 55 percent higher relative risk of cardiac events in women compared with men.

The researchers cited a few limitations of their analysis, including that they may have been influenced by publication bias. They also noted that sex differences in the association of atrial fibrillation with risk of death and cardiovascular disease may have been caused by unobserved confounding between the sexes. In addition, the studies had different designs, follow-up periods, outcomes and populations.

Further, they focused on the ratio of relative risks, which may not reflect absolute differences in the risk of death and cardiovascular disease associated with atrial fibrillation between the sexes. They also mentioned they could not determine the underlying causes of the sex differences in the association of atrial fibrillation with the risk of mortality and cardiovascular disease.