A new nationwide study in Denmark has shed light on the changing stroke risk in women versus men with atrial fibrillation (AF) over the period 1997-2020.

AF, a common type of irregular heart rhythm, increases the risk of stroke markedly due to blood pooling in the atria of the heart.

This can cause clots to form, and if they travel to the brain, this can block crucial blood flow and cause a stroke.

Female sex has long been considered a risk modifier for the relationship between stroke and AF, with women with AF exhibiting higher rates of stroke than men.

A study this month by Nielson and colleagues, published in Nature Communications, used Danish medical records to identify patients with an AF diagnosis between January 1997 and December 2020.

Patients with impaired renal function, valvular heart disease, oral anticoagulant treatment in the year before AF diagnosis or within 30 days after diagnosis, or who were 95 years or older, were excluded from the study.

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The CHA2DS2-VA score, which assesses stroke risk, was determined for all patients.

The calculation intentionally omitted sex as a variable, as treatment for AF differs notably by sex and is clinically relevant.

Stroke was determined using hospital records of thromboembolism, which includes both ischemic stroke and systemic embolism.

Researchers then assessed sex as an effect modifier.

A total of 158,982 Danish patients were included in the study, and 7,538 thromboembolic events (blood clot-related events) were recorded.

The risk of a thromboembolic event was highest between 1997-2000 with a risk of 5.6%, and lowest between 2013-16 with a risk of 3.8%.

The risk of a thromboembolic event overall has shown a consistent decline over the last 20 years in Denmark.

Initially, women had a 1.16 times higher relative risk of stroke compared to men in 1997-2000, but this difference decreased over time to 1.05 in 2017-2020, though this decrease was not significant.

This decrease in stroke may be due to modern management practices for stroke and AF, which include more timely and frequent prescribing of oral anticoagulant treatment for women.

Despite an increase in the proportion of women prescribed oral anticoagulant treatment over the study period, women are still less likely to receive oral anticoagulant treatment, which may, at least partially, explain the difference in the relative risk of stroke.

Leading data and analytics company GlobalData’s epidemiology forecast for AF and stroke shows in 2032, there will be more than 29 million diagnosed prevalent cases of AF across the 16 major markets (16MM: the US, France, Germany, Italy, Spain, the UK, Japan, Australia, Brazil, Canada, China, India, Japan, Mexico, Russia, South Africa, and South Korea).

An additional ten million AF cases are anticipated to go undiagnosed across the 16MM in 2032.

According to GlobalData’s epidemiology forecast, diagnosed incident cases of ischemic stroke are projected to increase at an annual growth rate of 3.24% from 2022 to 2032.

This data illustrates the scale of these indications and the expected increase in thromboembolic events despite the decreasing rates of stroke described in the study.

This data may appear to conflict, but in fact suggests that while rates of stroke due to AF are decreasing, overall numbers of strokes are not.

The ageing populations are likely the key driver of this trend, as the risk of stroke increases with age and an ageing population means a larger proportion of people will fall into this higher-risk segment of the population.

Improved diagnosis of AF and disease management will help mitigate the anticipated increase in stroke over the 2024-2032 period.

Without the effect modification by sex, sex differences in outcomes in AF patients in regard to stroke are expected to diminish worldwide.

Increased research into sex differences outside the Danish context, however, is needed to determine if this effect is local to Denmark, or perhaps more widespread across high-income markets.

Regardless, this study illustrates the changing epidemiology of AF and stroke and reinforces a need to investigate this changing relationship.