Before Age 35, Women More Vulnerable to Ischemic Stroke Than Men

Among adults younger than 35, women are at a 44% higher risk than men of having an ischemic stroke, according to a newly published systematic review. The same gap wasn’t seen for those ages 36 to 45.

The authors of the paper say their results suggest that sex-specific characteristics particular to this stage of life, such as pregnancy, may be at play.

“An assertion that young women may be disproportionately at risk of ischemic stroke represents a significant departure from our current scientific understanding and may have important implications about the cause of ischemic strokes in young adults,” they write in the February 2022 issue of Stroke.

Senior author Sharon N. Poisson, MD (University of Colorado Anschutz Medical Campus, Aurora), said this is a “challenging area to study because stroke is just a lot less common in younger adults,” with the result that the demographic can be an “afterthought” in larger studies.

Yet the intersection between stroke risk and age is a compelling topic, she told TCTMD, especially when it comes to gender. “We know that traditional risk factors are more common in men. That’s why, in the past, the thought has been that at any given age men have more strokes than women,” Poisson explained, adding, “[Our analysis] confirms to us that there really is something different going on in this younger age group and more research needs to be done to try to figure that out better.”

Strokes can happen at any age. . . . Keeping an open mind towards that is important. Sharon N. Poisson

Led by Michelle H. Leppert, MD (University of Colorado School of Medicine, Aurora), the researchers searched PubMed for papers published between January 2008 and July 2021. They identified 19 studies (three that had overlapping data) that reported sex-specific information on stroke among young adults.

The 16 studies with unique data included 69,793 individuals, nearly half of whom were women. Nine of these didn’t find any sex difference for those 45 or younger, three showed increased risk of ischemic stroke for men among individuals ages 30 to 35 years, and four showed a higher risk of ischemic stroke for women among individuals ages 35 or younger.

By synthesizing the data, however, Leppert et al calculated that in the below-35 subset, ischemic stroke risk was increased for women versus men (incidence rate ratio [IRR] 1.44; 95% CI 1.18-1.76). This pattern was observed in studies across France, Canada, the Netherlands, and the United States. For ages 35 to 45 years, though, the sex difference was more narrow and didn’t reach statistical significance (IRR 1.08; 95% CI 0.85-1.38).

Prior research has shown that only 15% of ischemic strokes occur before age 50, with much “uncertainty surrounding sex differences,” the authors point out. They attribute this lack of clarity to studies’ small sample sizes, failure to differentiate among stroke types, and broad age categories.

Based on this analysis, it appears that stroke-risk patterns are in contrast to the common thinking about atherosclerotic disease, where prevalence is initially lower among premenopausal women thanks to endogenous estrogen, then rises after menopause.

“Ischemic strokes are often a sequela of atherosclerotic disease and are subject to the same cardiovascular risk factors as ischemic heart disease,” so to see higher risk for younger women is counterintuitive, they explain. “This finding suggests that the role of nonatherosclerotic risk factors (ie, maternal strokes, hormonal contraceptives, and migraine headaches) in young women may be more important, yet poorly understood risk factors for ischemic stroke.”

As to why they found risk to pivot beyond age 35, Poisson’s theory is that there’s a “crossover” period in middle adulthood, where things like hypertension, diabetes, and hyperlipidemia begin to overlap with lesser-known risks unique to the young.

She stressed that, going forward, researchers should be careful to collect data prospectively on stroke in young adults, with the knowledge that the condition may not be the same across the life span. For clinicians, too, “the takeaway is that strokes can happen at any age. . . . Keeping an open mind towards that is important,” said Poisson.