Hospitalization for infection and risk of acute ischemic stroke: the Cardiovascular Health Study

Abstract

Background and purpose: Little is known about the acute precipitants of ischemic stroke, although evidence suggests infections contribute to risk. We hypothesized that acute hospitalization for infection is associated with the short-term risk of stroke.

Methods: The case-crossover design was used to compare hospitalization for infection during case periods (90, 30, or 14 days before an incident ischemic stroke) and control periods (equivalent time periods exactly 1 or 2 years before stroke) in the Cardiovascular Health Study, a population-based cohort of 5888 elderly participants from 4 US sites. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by conditional logistic regression. Confirmatory analyses assessed hazard ratios of stroke from Cox regression models, with hospitalization for infection as a time-varying exposure.

Results: During a median follow-up of 12.2 years, 669 incident ischemic strokes were observed in participants without a baseline history of stroke. Hospitalization for infection was more likely during case than control time periods; for 90 days before stroke, OR=3.4 (95% CI, 1.8 to 6.5). The point estimates of risks were higher when we examined shorter intervals: for 30 days, OR=7.3 (95% CI, 1.9 to 40.9), and for 14 days, OR=8.0 (95% CI, 1.7 to 77.3). In survival analyses, risk of stroke was associated with hospitalization for infection in the preceding 90 days, adjusted hazard ratio=2.4 (95% CI, 1.6 to 3.4).

Conclusions: Hospitalization for infection is associated with a short-term increased risk of stroke, with higher risks observed for shorter intervals preceding stroke.

Figure 1. Illustration of the case crossover design

The figure shows an example timeline illustrating case and control time periods for a hypothetical participant who enrolled in the study in January 1990 and had a stroke on December 30, 2004. The case period represents the 90 days prior to the stroke, excluding the 4 days immediately preceding the stroke, as infections during those dates were considered to possibly be secondary to stroke rather than preceding it. Control periods represent the same calendar periods 1 and 2 years prior to the stroke. More remote time periods were not included as their inclusion could add to bias due to participant aging in the case-crossover analyses, because participants serve as their own controls. Analyses then compared the prevalence of hospitalization for infection between case and both control time periods considered together. Analyses were repeated for 30 day and 14 day time windows.