Lifestyle, heart rate and cardiovascular disease: novel insights from genomics and big data

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, despite declining mortality rates due to improved treatment. Preventive strategies could be essential to reduce CVD burden, but will require a better understanding of the pathophysiological mechanisms underlying CVD development. Studying the genetic architecture of CVD and its risk factors might aid in this endeavor.
    Genome-wide association studies can increase our understanding of the underlying biological architecture of CVD and its risk factors by identifying associated genetic variants. These genetic variants can then be used to obtain generally unconfounded genetic associations between a risk factor and CVD.
    This thesis identifies novel genetic variants associated with prevalent lifestyle behaviors and several heart rate traits. We provide evidence that television watching might causally increase risk of coronary artery disease development. A genetic association between caffeine intake and CVD was not established. We find that heart rate at rest, its variability, its increase during exercise, and its recovery after exercise, are not likely on the causal pathway to mortality. We do find that higher genetically predicted resting heart rate decreases risk of atrial fibrillation, ischemic stroke and cardio-embolic stroke. The genetic association of resting heart rate with ischemic and cardio-embolic stroke is unlikely caused by resting heart rate itself, but is probably driven by the effect of resting heart rate associated variants on respectively pulse pressure and atrial fibrillation.
    The findings described in this thesis increase our insights in the pathophysiological mechanisms leading to CVD and may improve risk stratification and prevention strategies.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • van der Harst, Pim, Supervisor
    • Verweij, Niek, Co-supervisor
    Award date8-Jun-2022
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-6458-266-6
    DOIs
    Publication statusPublished - 2022

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