Infection as a Trigger for Acute Ischemic Stroke: The ARIC Study

Background and Purpose: Acute triggers for ischemic stroke, which may include infection, are poorly understood, as is whether background cardiovascular disease (CVD) risk modifies such triggering. We hypothesized that recent infection increases acute stroke risk, especially among those with low background CVD risk.

Methods: Hospitalized strokes and infections were identified during follow-up of the Atherosclerosis Risk in Communities (ARIC) cohort of 15,792 men and women aged 45-64 years at baseline (visit 1) in 1987-89 through 2013. A case-crossover design and conditional logistic regression were used to compare acute hospitalized infections among stroke patients (14, 30, 42, and 90 days prior to stroke) with corresponding control periods 1 year and 2 years prior. Background CVD risk was assessed using the ACC/AHA equations at both visit 1 and the visit most proximal to the stroke, with risk dichotomized at the median (10.0% estimated 10-year risk for visit 1 and 15.4% for most recent visit).

Results: A total of 1,008 adjudicated incident ischemic strokes were included. Compared to control periods 1 and 2 years before stroke, hospitalized infection was more common within 2 weeks before stroke (14 day odds ratio (OR) = 7.7 (95% confidence interval=2.1, 27.3)); the strength of association declined with increasing time in the exposure window before stroke (30 day OR = 5.7 (2.3, 14.3), 42 day OR = 4.5 (2.0, 10.2), and 90 day OR = 3.6 (2.1, 6.5) see Table). Stroke risk was higher among those with low compared with high background CVD risk, with this interaction (between hospitalized infection and CVD risk) reaching statistical significance for some exposure periods.

Conclusions: These results suggest that hospitalized infection is a trigger of ischemic stroke, and may explain some cryptogenic strokes. Infection control efforts may prevent some strokes. CVD preventive therapies, including antiplatelet agents and statins, may prevent strokes if used in the peri-infection period but clinical trials are needed to evaluate this.