Risk of Cardiovascular Events after Covid-19: a double-cohort study
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 a causal effect on all-cause mortality in a late post-COVID-19 period. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was partially supported by the National Heart Lung and Blood Institutes (NHLBI, grant number HL118277 to LGT), Medical Research Foundation of Oregon, and OHSU President Bridge funding (LGT). Oregon Clinical and Translational Research Institute grant (UL1TR002369) supported the use of REDCap. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of the Oregon Health & Science University gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. // 29.12.2021
