In a recent study posted to Research Square* preprint server, researchers examined the contribution of lifestyle and genetic factors to cardiovascular and thromboembolic event (CVE) risk following coronavirus disease 2019 (COVID-19).
Study: Contribution of genetics and lifestyle to the risk of major cardiovascular and thromboembolic complications following COVID-19. Image Credit: freshcare/Shutterstock
*Important notice: Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Background
Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and cardiovascular morbidity and mortality have increased lately owing to the COVID-19 pandemic. Preventing CVE is crucial during COVID-19 treatment. However, it is challenging to identify at-risk individuals for intensive surveillance and targeted prophylaxis.
Although prophylactic anticoagulation is recommended for patients hospitalized with COVID-19, there is conflicting evidence for use in more critical patients and ambulatory patients with mild COVID-19. General risk factors can help inform clinical practice but are not specific to the risk of CVE. Alternatively, the sum of genetic risk for a given trait, polygenic risk score (PRS), has been proposed for cardiovascular risk stratification.
About the study
In the present study, researchers assessed the association between lifestyle risk factors, PRSs, and the risk of CVE within 90 days following COVID-19. They enrolled participants with COVID-19 between March 2020 and September 2021 from the United Kingdom (UK) Biobank. Participants lacking baseline data on age, sex, body mass index, socioeconomic status, genotyping, and lifestyle factors were excluded.
The team used standard PRSs 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 status, physical activity, alcohol consumption, sleep and television viewing duration, and the intake of fruits/vegetables, oily fish, red meat, and processed meat.
The team used Cox proportional hazards model to examine the association between PRSs 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 deprivations (IMD), genotyping batch, and the first ten principal 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 analyses were also performed.
Findings
The researchers identified 25,335 individuals with COVID-19 from the UK Biobank eligible for inclusion. The mean age of participants was 65.9; most were White (84.6%) and female (52.7%). Overall, 8.6% of the COVID-19 cohort had an unhealthy lifestyle based on the composite lifestyle index, with the prevalence ranging from 10.8% for smoking to 48.5% for low intake of oily fish.
Post-COVID-19, 422 AF (1.67%), 135 VTE (0.53%), 244 CAD (0.96%), and 29 ISS (0.12%) events were recorded within 90 days. The incidence rate was estimated at 6.12, 28, 48.5, and 86.9 per 1000 person-years for ISS, VTE, CAD, and AF, respectively. A higher PRS for AF, VTE, or CAD was associated with an elevated risk for CVE post-COVID-19.
There was a dramatic increase in CVE outcomes in the first 15 – 30 days post-COVID-19. Participants with higher genetic risk showed a significantly higher CVE incidence after COVID-19 than those with low genetic risk. Individuals following a healthy lifestyle had a significantly lower risk of CAD, AF, and ISS in 90 days post-COVID-19 than those with an unhealthy lifestyle; this association was absent for post-COVID-19 VTE.
Around 5.86% of ISS, 2.95% of CAD, and 2.46% of AF could have been prevented if COVID-19 patients on unhealthy lifestyles had switched to healthy lifestyles. Notably, no significant interactions were found between lifestyle and genetic factors for any CVE outcome. Nonetheless, the team noted the additive effect of high genetic risk and unhealthy lifestyles on the increased risk of CAD and AF post-COVID-19. In general, sensitivity analyses yielded results consistent with the primary analysis.
Conclusions
The researchers observed that an increased genetic risk based on PRSs for CVE outcomes was associated with a higher incidence of CVE post-COVID-19. A healthy lifestyle among COVID-19 patients substantially reduces arterial events risk. Of note, around 11.4% of CVE outcomes could have been prevented if participants with unhealthy lifestyles followed a healthier lifestyle.
Taken together, the study observed that the genetic predisposition to CVE was associated with short-term risk of post-COVID-19 AF, CAD, and VTE, but not ISS and that healthier lifestyles can reduce the cardiovascular burden.
*Important notice: Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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