Systematic Review of Sex Differences in Ischemic Strokes Among Young Adults: Are Young Women Disproportionately at Risk?

Abstract

Background and purpose: Recent evidence suggests that young women (18-45 years) may be at higher risk of ischemic strokes than men of the same age. The goal of this systematic review is to reconcile and synthesize existing evidence of sex differences among young adults with ischemic strokes.

Methods: We searched PubMed from January 2008 to July 2021 for relevant articles and reviews and consulted their references. We included original studies that (1) were population based and (2) reported stroke incidence by sex or sex-specific incidence rate ratios of young adults ≤45 years. We excluded studies that (1) omitted measurements of error for incidence rates or incidence rate ratios, (2) omitted age adjustment, and (3) were not in English. Statistical synthesis was performed to estimate sex difference by age group (≤35, 35-45, and ≤45) and stroke type.

Results: We found 19 studies that reported on sex-specific stroke incidence among young adults, including 3 that reported on overlapping data. Nine studies did not find a statistically significant sex difference among young adults ≤45 years. Three studies found higher rates of ischemic stroke among men among young adults ≥30 to 35 years. Four studies found more women with ischemic strokes among young adults ≤35 years. Overall, in young adults ≤35 years, the estimated effect size favored more ischemic strokes in women (incidence rate ratio, 1.44 [1.18-1.76], I²=82%) and a nonsignificant sex difference in young adults 35 to 45 years (incidence rate ratio, 1.08 [0.85-1.38], I²=95%).

Conclusions: Overall, there were 44% more women ≤35 years with ischemic strokes than men. This gap narrows in young adults, 35 to 45 years, and there is conflicting evidence whether more men or women have ischemic strokes in the 35 to 45 age group.

Keywords: incidence; ischemic stroke; population; women; young adult.

Figure 1.

Age <35 years, Incidence rate ratio(women/men) of ischemic strokes with 95%CI for different populations and overall effect. Analyses of overall effect were performed with random effects models on the log of the ratio estimates. The combined ratios were estimated, along with 95%CI testing the null hypothesis of the IRR equaling one. *Study weights were calculated based on variability of the IRR.

Figure 2.

Age 35–45 years, Incidence rate ratios(women/men) of ischemic strokes with 95%CI for different populations and overall effect.

Figure 3.

Age ≤ 45 years. Incidence rate ratio(women/men) of ischemic strokes with 95%CI for different populations and overall effect.

Figure 4.

Forest plot of incidence rate ratio (IRR-men/women) by age group using a national US claims sample. IRR for Myocardial Infarctions(MI) in 15–24 is 3.38(2.05–5.57). Index ischemic stroke(IS) or MI is the first admission for IS or MI by ICD-9 code.