Women Face Greater Risk of Stroke-Related Mortality in Rheumatoid Arthritis Than Men

Findings from a recent study are providing clinicians with an overview of differences in the risk of stroke and stroke-related mortality in individuals with and without rheumatoid arthritis (RA), exploring potential sex-based differences in ischemic stroke, hemorrhagic stroke, and adverse outcomes.¹

The retrospective cohort study found individuals with RA had a greater risk of incident stroke, even after adjusting for cardiovascular risk factors and atrial fibrillation. Although there was no significant interaction between RA and sex for the risk of stroke, the effect of RA on stroke-related mortality differed significantly in women compared to men.¹

“With population aging, the burden of stroke is rising globally, with disproportionally worse outcomes in women. Previous studies report about 1.6-fold increased risk of stroke in people with rheumatoid arthritis compared to the general population,” Elena Myasoedova, MD, PhD, a clinical rheumatologist and associate professor of medicine at Mayo Clinic College of Medicine and Science, and colleagues wrote.¹ “Sex differences in the risk and outcomes of stroke in RA are not well understood.”

According to the World Health Organization, in 2019, 18 million people worldwide were living with RA, with women accounting for about 70% of this population.² As the disease progresses, symptoms of RA often spread beyond the joints, with about 40% of people who have RA also experiencing signs and symptoms that do not involve the joints.³ Although the association between stroke and RA is already recognized, less is known about potential sex-based differences in stroke risk and associated mortality in patients with RA.

To estimate the risk of incident stroke and stroke-related mortality in individuals with and without RA, both overall and by sex, investigators conducted a retrospective cohort study including residents of 8 counties in southeastern Minnesota with incident RA. For inclusion, individuals were required to be ≥ 18 years of age and fulfill ≥4 1987 ACR criteria for RA based on manual medical record review. Individuals who met the criteria in 1980-2014 and persons without RA from the same underlying population with similar age, sex, and calendar year of index were included.¹

All individuals were followed until death, migration, or the end of the study period on December 31, 2022. Incident cases of ischemic and hemorrhagic stroke were identified through manual record review. Excluding persons with stroke prior to RA incidence/index date, investigators used Cox proportional hazards models to compare incident stroke events in the RA versus the non-RA cohort, adjusting for demographics, smoking, and obesity.¹

The cumulative incidence of stroke was estimated, adjusting for the competing risk of death. Sex differences were also examined, and the underlying cause of death was obtained from government sources. Stroke-related mortality was compared in people with incident RA and persons without RA, and competing risk methods were used to compare cause-specific mortality between persons with RA and their matched comparators.¹

In total, the study included 2803 individuals with a mean age of 56.2 years. Among the cohort, 1402 persons had RA (68% women, 69% RF/CCP-positive) and 1401 individuals did not have RA (69% women).¹

The mean follow-up was 12.1 years in the RA cohort and 12.4 years in the non-RA cohort, during which incident ischemic strokes developed in 98 people with RA and 72 people without RA and incident hemorrhagic strokes developed in 20 people with RA and 14 people without RA. Adjusting for age and sex, investigators noted individuals with RA had a greater risk of incident ischemic stroke (hazard ratio [HR], 1.60; 95% CI, 1.18-2.17) and hemorrhagic stroke (HR, 1.65; 95% CI, 0.83-3.28). The association between RA and ischemic stroke remained significant after adjusting for cardiovascular risk factors and atrial fibrillation.¹

Further analysis revealed the cumulative incidence of any stroke in RA significantly outpaced that in non-RA beginning at 5 years of RA incidence (P = .015). Of note, there was no significant interaction between RA and sex for the risk of strokes. Investigators pointed out age at stroke incidence was similar in men and women with RA (median age 77.8 years in women vs 74.6 years in men), and similar to the non-RA individuals (79.6 years for women and 77.9 for men).¹

Investigators did not observe any difference in stroke-related mortality in the RA vs non-RA groups, with 42 stroke-related deaths in each group (HR, 1.22; 95% CI, 0.79-1.88). However, the effect of RA on stroke-related mortality differed significantly in women (HR, 1.85; 95% CI, 1.07-3.18) compared to men (HR, 0.54; 95% CI, 0.24-1.19; P = .009).¹

“The risk of stroke in RA is increased compared to the general population and is not fully explained by traditional risk factors or atrial fibrillation,” investigators concluded.¹ “There is no significant differential effect of sex on the association between RA and stroke risk overall or by subtype, but the association of RA and stroke-related mortality differs in women vs men.”

References

1. ^{Myasoedova E, Lennon R, Achenbach S, et al. ARE THERE SEX DIFFERENCES IN RISK AND OUTCOMES OF STROKE IN PATIENTS WITH RHEUMATOID ARTHRITIS? A POPULATION-BASED RETROSPECTIVE COHORT STUDY. EULAR. doi:10.1136/annrheumdis-2024-eular.2303}
2. ^{World Health Organization. Rheumatoid arthritis. Newsroom. June 28, 2023. Accessed June 27, 2024. https://www.who.int/news-room/fact-sheets/detail/rheumatoid-arthritis}
3. ^{Mayo Clinic. Rheumatoid Arthritis. Diseases & Conditions. January 25, 2023. Accessed June 27, 2024. https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648}