Modifiable Risk Factors and Attributable Burden of Cardiac Arrest: An Exposome-wide and Mendelian Randomization...

In this study, we aimed to identify nonclinical modifiable risk factors associated with sudden cardiac arrest (SCA) incidence, and to assess attributable burden.

Data on 125 potentially modifiable risk factors were extracted from the UK Biobank cohort. An exposome-wide association study was conducted using a Cox proportional hazard model, followed by validation of significant associations using Mendelian randomization to identify causal relationships. The attributable burden of SCA was evaluated on the basis of improvements in unfavourable profiles. We also evaluated the attributable burden to be eliminated via improvement of unfavourable profiles.

Of 502,094 individuals, 3147 developed SCA during a median follow-up duration of 13.8 years. SCA was associated with 56 risk factors spanning lifestyles, physical measures, psychosocial factors, socioeconomic status, and the local environment. Mendelian randomization analysis confirmed protective effects associated with 2 factors (ie, higher rates of consumption of champagne and/or white wine and fruit intake) and adverse effects associated with 7 factors (ie, time spent using the computer, fed-up feelings, greater arm fat mass and percentage, body mass index, systolic blood pressure, and lower education level). Between 40% (conservative elimination) and 63% (thorough elimination) of SCA cases could be prevented by improving unfavourable profiles, with lifestyle modifications accounting for the largest proportion of preventable cases, followed by improvements in physical measures, psychosocial factors, socioeconomic status, and the local environment.

This large-scale, prospective cohort study offers compelling evidence on the profile of modifiable risk factors and the attributable burden of SCA.