Elena Zapata-Arriaza, MD

Xu J, Yalkun G, Wang M, Wang A, Wangqin R, Zhang X, Chen Z, Mo J, Meng X, Li H, et al. Impact of Infection on the Risk of Recurrent Stroke Among Patients With Acute Ischemic Stroke. Stroke. 2020;51:2395–2403.

The association of immune changes after stroke and infection appearance has been widely evidenced recently. Inflammatory cascade occurring during infection may promote platelet, endothelial and coagulation changes triggering subsequent cerebrovascular events. Xu J et al. aim to investigate whether infection increases the short- and long-term risk of recurrent stroke in patients hospitalized due to acute ischemic stroke (AIS).

For the purpose, data were derived from ischemic stroke patients in 2 stroke registries (CSCA study and CNSR III study) realized in China. These registries recorded the medical data during hospitalization and finished 1-year follow-up. Associations of infection (pneumonia or urinary tract infection) during hospitalization with recurrent stroke in the short (during hospitalization) and long term (since 30 days to 1 year after stroke onset) were analyzed. The primary outcome was recurrent stroke, and secondary outcomes included the recurrence of ischemic stroke, intracerebral hemorrhage, hemorrhagic transformation, myocardial infarction, combined vascular events (including recurrent stroke, myocardial infarction, and vascular death), and all cause death. In the CSCA, the authors conducted multivariate logistic regression models to investigate the association of infection with in-hospital outcomes. To keep consistency and confirm the finding in the CSCA, the association of infection with in-hospital outcomes in the CNSR-III was analyzed using logistic regression models.

After data analysis, in the CSCA (n=789 596), the incidence of infection during hospitalization was 9.6%. Patients with infection had a higher risk of stroke recurrence during hospitalization compared with patients without infection (10.4% versus 5.2%; adjusted odds ratio, 1.70 [95% CI, 1.65–1.75]; P<0.0001). In the CNSR-III (n=13 549), the incidence of infection during hospitalization was 6.5%. Infection during hospitalization was significantly associated with short-term risk of recurrent stroke (7.4% versus 3.9%; adjusted odds ratio, 1.40 [95% CI, 1.05–1.86]; P=0.02), but not with long-term risk of recurrent stroke (7.2% versus 5.2%; adjusted hazard ratio, 1.16 [95% CI, 0.88–1.52]; P=0.30). In the sensitivity analysis, the impact of pneumonia on clinical outcomes remained similar to the major analysis, but urinary tract infection was not associated with stroke recurrence in the short or long term. Finally , patients with prestroke infection had a higher risk of stroke recurrence during hospitalization whether or not adjusting for hs-CRP on admission.

This article has demonstrated that infection after cerebrovascular event was related to stroke recurrence, hemorrhagic transformation, combined vascular events and all-cause deaths during admission, but not in the long term after hospitalization. Furthermore, prestroke infection within 2 weeks of stroke onset was associated with an increased risk of recurrent stroke during hospitalization.

These findings highlight the importance of infection in the prognosis of stroke, beyond the ischemic damage itself. The infection is, in turn, a consequence and may become the cause of a new stroke. Pneumonia is the medical complication with the greatest impact on patient mortality, and based on the results of this article, its impact extends to other complications after stroke. The published results highlight the relevance of infection after stroke and the need to address the immune changes that occur after ischemia. The inflammatory cascade triggered after the stroke has a scope beyond the infection itself, as it may be influencing endothelial and vascular wall changes that facilitate hemorrhagic transformation, the new ischemic stroke or death from all causes. Taking into account the failures in the prophylactic tests of the infection after the stroke and the impact of the same in the prognosis of the stroke, we should be considering a change in the paradigm of diagnosis and therapeutic management of this medical complication, with the aim of reduce its impact on the patient’s final clinical outcome.