Lifestyle and genetic factors influence the risk of cardiovascular complications after COVID-19

In a recent study published on Research Square* Preprint server, Researchers investigated the contribution of lifestyle and genetic factors to the risk of cardiovascular and thromboembolic events (CVE) after coronavirus disease 2019 (COVID-19).

Study: Contribution of genetics and lifestyle to the risk of major cardiovascular and thromboembolic complications after COVID-19.  Image Credit: freshcare/Shutterstock
Study: Contribution of genetics and lifestyle to the risk of major cardiovascular and thromboembolic complications after COVID-19. Image Credit: freshcare/Shutterstock


Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and cardiovascular morbidity and mortality have recently increased due to the COVID-19 pandemic. Prevention of CVE is crucial during the treatment of COVID-19. However, it is challenging to identify at-risk individuals for intensive monitoring and targeted prophylaxis.

Although prophylactic anticoagulation is recommended for hospitalized patients with COVID-19, there is conflicting evidence for use in more critically ill patients and outpatients with mild COVID-19. General risk factors can help inform clinical practice but are not specific for CVE risk. Alternatively, a sum of genetic risk for a given trait, the polygenic risk score (PRS), has been proposed for cardiovascular risk stratification.

About studying

In this study, researchers assessed the association between lifestyle risk factors, PRS, and CVE risk during the 90 days after COVID-19. They enrolled participants with COVID-19 between March 2020 and September 2021 from the United Kingdom (UK) Biobank. Participants missing baseline data on age, gender, body mass index, socioeconomic status, genotyping, and lifestyle factors were excluded.

The team used the standard PRS for coronary artery disease (CAD), ischemic stroke (ISS), venous thromboembolic disease (VTE) and atrial fibrillation (AF) in the primary analysis. A composite healthy lifestyle index was defined by aggregating data on smoking, physical activity, alcohol consumption, sleep and length of television viewing, and intake of fruit/vegetables, fatty fish, red meat, and processed meat.

The team used a Cox proportional hazards model to examine the association between PRS and corresponding CVE outcomes (AF, CAD, VTE, and ISS). Hazard ratios and associated 95% confidence intervals were derived after adjusting for sex, age, education level, index of multiple deprivation (IMD), genotyping lot, and the first ten major components of genetic ancestry.

A multivariable Cox regression model was used for the overall cohort for lifestyle factors and across PRS categories. The combined effect of lifestyle and genetics was estimated on CVE outcomes statistically associated with lifestyle and genetic factors. Finally, several sensitivity analyzes were also performed.


The researchers identified 25,335 individuals with COVID-19 from the UK Biobank eligible for inclusion. The average age of the participants was 65.9; the majority were white (84.6%) and female (52.7%). Overall, 8.6% of the COVID-19 cohort had an unhealthy lifestyle based on a composite lifestyle index, with prevalence ranging from 10.8% for smoking to 48.5% for low fatty fish intake.

After COVID-19, 422 AF (1.67%), 135 VTE (0.53%), 244 CAD (0.96%) and 29 ISS (0.12%) were recorded within 90 days. The incidence was estimated to be 6.12, 28, 48.5 and 86.9 per 1000 person-years for ISS, VTE, CAD and FS, respectively. A higher PRS for AF, VTE, or CAD was associated with an increased risk of CVE after COVID-19.

In the first 15-30 days after COVID-19, there was a dramatic increase in CVE results. Participants with higher genetic risk showed a significantly higher incidence of CVE after COVID-19 than those with low genetic risk. Individuals with a healthy lifestyle had a significantly lower risk of CHD, FS, and ISS during the 90 days after COVID-19 than those with an unhealthy lifestyle; this association was absent in VTE after COVID-19.

Approximately 5.86% of ISS, 2.95% of CAD and 2.46% of FS could be prevented if COVID-19 patients with unhealthy lifestyles switched to healthy lifestyles. In particular, no significant interactions between lifestyle and genetic factors were found for any CVE outcome. However, the team noted an additive effect of high genetic risk and unhealthy lifestyle on the increased risk of CAD and AF after COVID-19. In general, sensitivity analyzes yielded results consistent with the primary analysis.


The researchers observed that increased PRS-based genetic risk for CVE outcomes was associated with a higher incidence of CVE after COVID-19. A healthy lifestyle in patients with COVID-19 significantly reduces the risk of arterial events. Of note, approximately 11.4% of CVE outcomes could have been prevented if participants with unhealthy lifestyles had followed a healthier lifestyle.

Overall, the study found that genetic predisposition to CVE was associated with short-term risk of post-COVID-19 AF, CAD, and VTE, but not ISS, and that a healthier lifestyle can reduce cardiovascular burden.

*Important notice

Research Square publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guiding clinical practice/health-related behavior, nor should they be treated as verified information.

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