Walter Valesky, MD
Purroy F, Vicente-Pascual M, Arque G, Baraldes-Rovira M, Begue R, Gallego Y, Gil MI, Gil-Villar MP, Mauri G, Quilez A, et al. Sex-Related Differences in Clinical Features, Neuroimaging, and Long-Term Prognosis After Transient Ischemic Attack. Stroke. 2021;52:424–433.
Stroke affects more women than men. This gender preponderance has been attributed to longevity of women, putting them at higher risk of stroke. The gender differences are poorly reported in the literature for transient ischemic attack (TIA). The few studies that have addressed the gender differences in TIA have mainly focused on presentation nuances between men and women, initial management, and stroke recurrence rates of up to 1 year.1-2 Purroy et al. attempt to give greater insight into this issue by following a cohort of patients diagnosed with TIA for up to 10 years.
The authors analyzed data on 723 consecutive patients with TIA presenting to the emergency department after exclusion of mimics. These patients were admitted to the neurology service with a median ABCD2 score of 5. TIA was defined as transient neurologic deficits lasting less than 24 hours. Approximately 40% of these patients underwent imaging that was diffusion-weighted imaging (DWI) positive on MRI within 7 days of symptom onset. The diagnostic evaluation for stroke was notable in that extra- and intracranial ultrasound was utilized for vascular imaging rather than CTA or MRA. The primary outcome was recurrent ischemic stroke defined by new neurological symptoms associated with changes on neuroimaging.
Baseline characteristics were notable for women being older (72.4 years vs. 69.5 years; p=0.001) and having lower rates of peripheral vascular disease (1.7% vs 5%; p=0.024) and active smoking (5% vs 20.7%; p= <0.001) than men. Women also presented with more than twice the number of non-definitive TIA events at baseline (16.2% vs. 7.1%; p=0.001). As for TIA etiology, women had a higher prevalence of undetermined causes compared to men (42.1% vs. 34.4%; p=0.037) but a smaller prevalence of large artery atherosclerosis (LAA) (11.9% vs. 21.1%; p=0.001).
The primary outcome demonstrated no difference in recurrent ischemic stroke between women and men, 14.3% vs 12.6%, respectively, with ~15% of these recurrent strokes occurring 6 years or more after the index TIA. A secondary composite outcome of acute coronary syndrome, ischemic stroke, development of peripheral artery disease, and death from cardiovascular causes was significantly lower in women than men (17.5% vs. 23.8%; p=0.044).
Several findings can be taken away from this data. It supports prior authors’ conclusions that, generally, women presenting with TIA are older and less likely to suffer from heart disease, myocardial infarction, and peripheral artery disease than men.3 Additionally, LAA was the only TIA etiology associated with stroke recurrence in women despite the fact that this etiology was responsible for the lowest percentage of TIA presentations. Last, as in prior studies, the authors note that women are associated with atypical TIA presentations; this was not associated with a decreased risk of stroke recurrence (HR 0.15; p=0.059).1-2 However, it is possible that this data is underpowered.
It has been shown that tissue-based prognostication for TIA and minor stroke more accurately predicts clinical endpoints such as recurrent stroke and death than time-based endpoints.4 In Purroy et al., this held true for women but not for men. This could be explained by the significant number of atypical TIA presentations in women and due to the higher number of TIAs with undetermined causes. Therefore, clinicians may want to consider a lower threshold to obtain DWI for women with suspected TIA or atypical symptoms.
In Purroy et al., the median ABCD2 score was 5. Therefore, this data may not be applicable with less severe TIAs. Also, as LAA is associated with stroke recurrence despite significantly lower prevalence than men, this allows a high-yield opportunity for treatment. Unfortunately, prior investigators have shown that women are less likely to be offered medications such as statins in comparison with men.5 Clinicians should be mindful of these gender biases when managing these patients.
1. Yu AYX, Penn AM, Lesperance ML, et al. Sex Differences in Presentation and Outcome After an Acute Transient or Minor Neurologic Event. JAMA Neurol. 2019;76(8):962. doi:10.1001/jamaneurol.2019.1305
2. Li OL, Silver FL, Lichtman J, et al. Sex Differences in the Presentation, Care, and Outcomes of Transient Ischemic Attack: Results From the Ontario Stroke Registry. Stroke. 2016;47(1):255-257. doi:10.1161/STROKEAHA.115.010485
3. Reeves MJ, Bushnell CD, Howard G, et al. Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes. The Lancet Neurology. 2008;7(10):915-926. doi:10.1016/S1474-4422(08)70193-5
4. Hurford R, Li L, Lovett N, et al. Prognostic value of “tissue-based” definitions of TIA and minor stroke: Population-based study. Neurology. 2019;92(21):e2455-e2461. doi:10.1212/WNL.0000000000007531
5. Nanna MG, Wang TY, Xiang Q, et al. Sex Differences in the Use of Statins in Community Practice. Circ Cardiovasc Qual Outcomes. 2019;12(8):e005562. doi:10.1161/CIRCOUTCOMES.118.005562