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

Int J Epidemiol. 2020 Feb 1;49(1):162-172. doi: 10.1093/ije/dyz212.


Background: The advent of very large cohort studies (n > 500 000) has given rise to prospective analyses of health outcomes being undertaken after short (<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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Exercise; bias; epidemiologic methods; follow-up studies; physical activity; prospective studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality
  • Causality
  • Cohort Studies
  • Exercise / physiology*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Life Style*
  • Male
  • Middle Aged
  • Mortality*
  • Neoplasms / epidemiology*
  • Neoplasms / etiology
  • Neoplasms / mortality
  • Prospective Studies
  • Time Factors