Risk Factors for Stroke in Patients With Sepsis and Bloodstream Infections

Iris Yuefan Shao, MPH; Mitchell S.V. Elkind, MD, MS; Amelia K. Boehme, PhD, MSPH

Disclosures

Stroke. 2019;50(5):1046-1051. 

In This Article

Abstract and Introduction

Abstract

Background and Purpose: Sepsis has been identified as a trigger for stroke, but the underlying mechanisms and risk factors that predispose patients with sepsis to increased stroke risk remain unclear. We sought to identify predictors of stroke after sepsis and bloodstream infections.

Methods: The 2007–2009 California State Inpatient Database from the Health Care Utilization Project was used to identify patients over the age of 18 years and hospitalized with sepsis or bloodstream infection defined by International Classification of Diseases, Ninth Revision codes. Patients who died during their sepsis hospitalization were excluded. The primary outcome was a primary diagnosis of ischemic or hemorrhagic stroke on a subsequent hospitalization within 1 year. Associations between risk factors, also defined by International Classification of Diseases, Ninth Revision codes, and stroke were analyzed using multivariable logistic regression. A composite risk score was generated to predict stroke risk.

Results: Of 121 947 patients with sepsis, 0.5% (n=613) had a primary diagnosis of stroke within a year of their sepsis hospitalization. Significant predictors for stroke were identified. A score was generated from these risk factors with points assigned based on regression coefficients: valvular heart diseases (1 point), congestive heart failure (1), renal failure (1), lymphoma (2), peripheral vascular diseases (2), pulmonary circulation disorders (2), and coagulopathy (3). The C statistic for the receiver operating characteristic curve for the score was 0.68. The risk of stroke increased 43% (odds ratio, 1.43; 95% CI, 1.37–1.48) per-point increase in the score. The effect of increase in score was greater among younger patients.

Conclusions: Risk factors and a composite risk score for stroke may help identify a subpopulation of sepsis patients that could be targeted to reduce the short-term risk of stroke after serious infections.

Introduction

Stroke remains the leading cause of serious long-term adult disability in the United States and incurs a huge cost from both clinical and societal perspectives.[1] Though stroke mortality has declined substantially over the past decade due to effective combinations of prevention and intervention programs, the decline in incidence and prevalence of stroke has recently begun to reverse, and there is evidence that stroke is increasing in younger individuals.[2,3] Traditional cardiovascular risk factors do not fully account for the risk of stroke, moreover, and they also fail to explain why strokes occur at a particular vulnerable point in time. Therefore, it is a high priority to identify novel risk factors of long-term risk, as well as triggers associated with short-term risk, to better prevent stroke.

One such novel risk factor may be sepsis. Recent evidence has suggested that infections, including sepsis, could function as acute triggers for stroke, increasing stroke risk within a relatively short period of time.[4–9] Sepsis is a leading cause of death in the United States, particularly among patients in the intensive care unit.[6] Sepsis patients are at long-term increased risk of death and major adverse cardiovascular events.[7] Additionally, sepsis is associated with an increased intermediate and long-term risk for stroke.[5,8,9] The risk of stroke after sepsis appears to be higher in younger sepsis patients, and in patients who do not have diabetes mellitus, but these associations and interactions need further exploration.[10] Possible mechanisms linking sepsis to stroke could be atrial fibrillation, hemodynamic instability, coagulopathy, the systemic inflammatory response syndrome, and prolonged inflammation.[8] It is therefore important to identify which patients are at highest risk for stroke after sepsis and bloodstream infection for risk management purposes. In this study, we aimed to identify those patients at greatest risk of stroke after their sepsis hospitalization.

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