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Sepsis hospitalization and risk of subsequent cardiovascular events in adults: a population-based matched cohort study

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Abstract

Purpose

To determine whether surviving a first sepsis hospitalization is associated with long-term cardiovascular events.

Methods

Population-based matched cohort study conducted in Ontario, Canada (2008–2017). Adult survivors (older than 18 years) of a first sepsis hospitalization were matched to adult survivors of a non-sepsis hospitalization using hard-matching and propensity score methods. Patients with pre-existing cardiovascular disease were excluded. The primary composite outcome was myocardial infarction, stroke, or cardiovascular death up to 5 years of follow-up. Secondary outcomes included venous thromboembolism and all-cause death. Cox proportional hazards models with robust standard errors were used to estimate the association of sepsis with all outcomes of interest; hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Sensitivity analyses included Fine and Gray models to account for the competing risk of all-cause death and probabilistic bias analyses.

Results

254,241 adult sepsis survivors were matched to adult survivors of non-sepsis hospitalization episodes. Sepsis survivors experienced an increased hazard of major cardiovascular events compared to non-sepsis survivors (HR 1.30; 95% CI 1.27–1.32), which was more pronounced in younger patients (HR 1.66; 95% CI 1.36–2.02 for patients aged 40 or younger; HR 1.21; 95% CI 1.18–1.24 for patients older than 80 years). Sepsis survivors also faced an increased hazard of venous thromboembolism (HR 1.61; 95% CI 1.55–1.67) and all-cause death (HR 1.26; 95% CI 1.25–1.27). Sensitivity analyses yielded consistent results.

Conclusions

Adult sepsis survivors experience an increased hazard of major cardiovascular events compared to survivors of a non-sepsis hospitalization.

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Data and code availability

The dataset from this study is held securely in coded form at ICES. While data sharing agreements prohibit ICES from making the dataset publicly available, access may be granted to those who meet pre-specified criteria for confidential access, available at www.ices.on.ca/DAS. The full dataset creation plan and underlying analytic code are available from the authors upon request, understanding that the computer programs may rely upon coding templates or macros that are unique to ICES and are therefore either inaccessible or may require modification.

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Acknowledgements

This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). Parts of this material are based on data and/or information compiled and provided by CIHI. However, the analyses, conclusions, opinions, and statements expressed in the material are those of the author(s), and not necessarily those of CIHI. Parts of this report are based on Ontario Registrar General (ORG) information on deaths, the original source of which is ServiceOntario. The views expressed therein are those of the author and do not necessarily reflect those of ORG or the Ministry of Government and Consumer Services. FA is partially supported by a Vanier Canada Graduate Scholarship from the Canadian Institutes of Health Research and a Research Award from the Interdepartmental Division of Critical Care Medicine at the University of Toronto. HW is partially supported by a Canada Research Chair [Tier 2] in Critical Care Organization and Outcomes. Dr. Dennis Ko is supported by a Jack Tu Chair in Cardiovascular Outcomes Research, Sunnybrook Hospital and University of Toronto. Dr. Lawler is partially supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada. The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred. We thank Bruno Ferreyro for his comments on a previous version of the present analysis.

Funding

Funding was provided by Canadian Institutes of Health Research (Grant no. 169865).

Author information

Authors and Affiliations

  1. Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Federico Angriman, Hannah Wunsch & Damon C. Scales

  2. Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada

    Federico Angriman, Patrick R. Lawler, Hannah Wunsch & Damon C. Scales

  3. Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

    Federico Angriman, Hannah Wunsch & Damon C. Scales

  4. Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

    Laura C. Rosella

  5. ICES, Toronto, Canada

    Laura C. Rosella, Dennis T. Ko, Hannah Wunsch & Damon C. Scales

  6. Peter Munk Cardiac Centre, University Health Network, Toronto, Canada

    Patrick R. Lawler

  7. Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Canada

    Dennis T. Ko

  8. Institute for Better Health, Trillium Health Partners, Mississauga, ON, Canada

    Laura C. Rosella

  9. Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, Toronto, ON, Canada

    Laura C. Rosella

Authors
  1. Federico Angriman
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  2. Laura C. Rosella
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  3. Patrick R. Lawler
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  4. Dennis T. Ko
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  5. Hannah Wunsch
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  6. Damon C. Scales
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Contributions

All authors contributed to the study conception and design. Material preparation and data analysis were completed by FA, LR, HW, and DCS. All authors contributed to data interpretation. The first draft of the manuscript was written by FA and DCS. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Federico Angriman.

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Angriman, F., Rosella, L.C., Lawler, P.R. et al. Sepsis hospitalization and risk of subsequent cardiovascular events in adults: a population-based matched cohort study. Intensive Care Med 48, 448–457 (2022). https://doi.org/10.1007/s00134-022-06634-z

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