Risk of Cardiovascular Events after Covid-19: a double-cohort study

  1. Larisa G. Tereshchenko
  2. Adam Bishop
  3. Nora Fisher-Campbell
  4. Jacqueline Levene
  5. Craig C. Morris
  6. Hetal Patel
  7. Erynn Beeson
  8. Jessica A. Blank
  9. JG N. Bradner
  10. Michelle Coblens
  11. Jacob W. Corpron
  12. Jenna M. Davison
  13. Kathleen Denny
  14. Mary S. Earp
  15. Simeon Florea
  16. Howard Freeman
  17. Olivia Fuson
  18. Florian Guillot
  19. Kazi Haq
  20. Jessica Hyde
  21. Ayesha Khader
  22. Clinton Kolseth
  23. Morris Kim
  24. Olivia Krol
  25. Lisa Lin
  26. Liat Litwin
  27. Aneeq Malik
  28. Evan Mitchell
  29. Aman Mohapatra
  30. Cassandra Mullen
  31. Chad D Nix
  32. Ayodele Oyeyemi
  33. Christine Rutlen
  34. Lisa Corley-Stampke
  35. Ashley Tam
  36. Inga Van Buren
  37. Jessica Wallace
  38. Akram Khan
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Abstract

Objective

To determine absolute and relative risks of either symptomatic or asymptomatic SARS-CoV-2 infection for late cardiovascular events and all-cause mortality.

Methods

We conducted a retrospective double-cohort study of patients with either symptomatic or asymptomatic SARS-CoV-2 infection [COVID-19(+) cohort] and its documented absence [COVID-19(-) cohort]. The study investigators drew a simple random sample of records from all Oregon Health & Science University (OHSU) Healthcare patients (N=65,585) with available COVID-19 test results, performed 03.01.2020 - 09.13.2020. Exclusion criteria were age < 18y and no established OHSU care. The primary outcome was a composite of cardiovascular morbidity and mortality. All-cause mortality was the secondary outcome.

Results

The study population included 1355 patients (mean age 48.7±20.5 y; 770(57%) female, 977(72%) white non-Hispanic; 1072(79%) insured; 563(42%) with cardiovascular disease (CVD) history). During a median 6 months at risk, the primary composite outcome was observed in 38/319 (12%) COVID-19(+) and 65/1036 (6%) COVID-19(-) patients (p=0.001). In Cox regression adjusted for demographics, health insurance, and reason for COVID-19 testing, SARS-CoV-2 infection was associated with the risk of the primary composite outcome (HR 1.71; 95%CI 1.06-2.78; p=0.029). Inverse-probability-weighted estimation, conditioned for 31 covariates, showed that for every COVID-19(+) patient, the average time to all-cause death was 65.5 days less than when all these patients were COVID-19(-): average treatment effect on the treated -65.5 (95%CI -125.4 to -5.61) days; p=0.032.

Conclusions

Either symptomatic or asymptomatic SARS-CoV-2 infection is associated with increased risk of late cardiovascular outcomes and has causal effect on all-cause mortality in a late post-COVID-19 period.

<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</ext-link> Identifier: <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04555187">NCT04555187</ext-link>

Key messages

What is already known about this subject

  • Acute, symptomatic COVID-19 can cause acute cardiovascular manifestations.

  • Post-acute or “long” COVID-19 can be a debilitating disease following acute infection with a heterogenous presentation.

What might this study add?

  • Either symptomatic or asymptomatic SARS-CoV-2 infection is associated with increased risk of late cardiovascular outcomes.

  • Either symptomatic or asymptomatic SARS-CoV-2 infection has causal effect on all-cause mortality in a late post-COVID-19 period.

How might this impact on clinical practice?

  • As we begin to care for more survivors of COVID-19, we will need to better understand not only how to care for their acute symptoms and complications following infection, but also recognize future cardiovascular risk and mitigate such risk with appropriate screening and preventative measures.

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