Impact of follow-up time and analytical approaches to account for reverse causality on the association between physical activity and health outcomes in UK Biobank

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  • Tessa Strain
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
  • Katrien Wijndaele
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
  • Stephen J Sharp
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
  • Paddy C Dempsey
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
  • Nick Wareham
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
  • Søren Brage
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK

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<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>The advent of very large cohort studies (n &gt; 500 000) has given rise to prospective analyses of health outcomes being undertaken after short (&lt;4 years) follow-up periods. However, these studies are potentially at risk of reverse causality bias. We investigated differences in the associations between self-reported physical activity and all-cause and cardiovascular disease (CVD) mortality, and incident CVD, using different follow-up time cut-offs and methods to account for reverse causality bias.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Data were from n = 452 933 UK Biobank participants, aged 38–73 years at baseline. Median available follow-up time was 7 years (for all-cause and CVD mortality) and 6.1 years (for incident CVD). We additionally analysed associations at 1-, 2- and 4-year cut-offs after baseline. We fit up to four models: (1) adjusting for prevalent CVD and cancer, (2) excluding prevalent disease, (3) and (4) Model 2 excluding incident cases in the first 12 and 24 months, respectively.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>The strength of associations decreased as follow-up time cut-off increased. For all-cause mortality, Model 1 hazard ratios were 0.73 (0.69–0.78) after 1 year and 0.86 (0.84–0.87) after 7 years. Associations were weaker with increasing control for possible reverse causality. After 7-years follow-up, the hazard ratios were 0.86 (0.84–0.87) and 0.88 (0.86–0.90) for Models 1 and 4, respectively. Associations with CVD outcomes followed similar trends.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>As analyses with longer follow-up times and increased control for reverse causality showed weaker associations, there are implications for the decision about when to analyse a cohort study with ongoing data collection, the interpretation of study results and their contribution to meta-analyses.</jats:p> </jats:sec>

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