Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank

Abstract

Objective: To examine association of COVID-19 with incident cardiovascular events in 17 871 UK Biobank cases between March 2020 and 2021.

Methods: COVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32-395) of prospective follow-up.

Results: Non-hospitalised cases (n=14 304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period.

Conclusions: Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.

Keywords: COVID-19; epidemiology.

Figure 1

Flow chart of participant selection.

Figure 2

Summary of study design and results. AF, atrial fibrillation; CVD, cardiovascular disease; IHD, ischaemic heart disease; MI, myocardial infarction; VTE, venous thromboembolism. Red bars indicate statistically significant associations (p<0.05).

Figure 3

Histograms of event time for all incident outcomes. Blue bars represent incident events in COVID-19 cases, while the red bars indicate those in matched controls. AF, atrial fibrillation; CVD, cardiovascular disease; HF, heart failure; IHD, ischaemic heart disease; MI, myocardial infarction; VTE, venous thromboembolism.