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Examining associations between physical activity and cardiovascular mortality using negative control outcomes

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journal contribution
posted on 08.11.2018, 10:00 authored by Mark Hamer, Adrian Bauman, Joshua A. Bell, Emmanuel Stamatakis
Background: The purpose of a negative control is to reproduce a condition that cannot involve the hypothesized causal mechanism, but does involve the same sources of bias and confounding that may distort the primary association of interest. Observational studies suggest physical inactivity is a major risk factor for cardiovascular disease (CVD) although potential sources of bias, including reverse causation and residual confounding, make it difficult to infer causality. The aim was to employ a negative control outcome to explore the extent to which the association between physical activity and CVD mortality is explained by confounding. Methods: The sample comprised 104,851 participants (aged 47 ± 17 yrs; 45.4% male) followed up over mean [SD] 9.4±4.5 years, recruited from The Health Survey for England and the Scottish Health Surveys. Results: There were 10,309 deaths, of which 3,109 were attributed to CVD, and 157 to accidents (negative control outcome). Accidental death was related to age, male sex, smoking, longstanding illness and psychological distress, with some evidence of social patterning. This confounding structure was similar to that seen with CVD mortality, suggesting that our negative control outcome was appropriate. Physical activity (per SD unit increase in MET-hr-wk) was inversely associated with CVD (HR=0.75; 95% CI, 0.70, 0.80); the point estimate between physical activity and accidental death was in the same direction but of lesser magnitude (HR=0.86; 0.69, 1.07). A linear dose-response pattern was observed for physical activity and CVD but not with the negative control. Conclusions: Inverse associations between physical activity and risk of CVD mortality are likely causal but of a smaller magnitude than commonly observed. Negative control studies have potential to improve causal inference within the physical activity field.

Funding

Stamatakis is funded by the National Health and Medical Research Council (NHMRC) through a Senior Research Fellowship. Hamer is funded through the NIHR Leicester BRC; Bell through CRUK (C18281/A19169).

History

School

  • Sport, Exercise and Health Sciences

Published in

International Journal of Epidemiology

Volume

48

Issue

4

Pages

1161 - 1166

Citation

HAMER, M. ... et al, 2018. Examining associations between physical activity and cardiovascular mortality using negative control outcomes. International Journal of Epidemiology, 48 (4), pp.1161-1166.

Publisher

© the Authors. Published by Oxford University Press on behalf of the International Epidemiological Association

Version

AM (Accepted Manuscript)

Publisher statement

This is a pre-copyedited, author-produced version of an article accepted for publication in International Journal of Epidemiology following peer review. The version of record HAMER, M. ... et al, 2018. Examining associations between physical activity and cardiovascular mortality using negative control outcomes. International Journal of Epidemiology, 48 (4), pp.1161-1166 is available online at: https://academic.oup.com/ije/article/48/4/1161/5238845 and https://doi.org/10.1093/ije/dyy272.

Acceptance date

01/11/2018

Publication date

2018-12-11

ISSN

0300-5771

eISSN

1464-3685

Language

en