Dose-response associations between accelerometry measured physical activity and sedentary time with all-cause mortality: a systematic review and harmonised meta-analysis

Objective: To examine the dose-response associations between accelerometer assessed total physical activity, different intensities of activity, and sedentary time with all-cause mortality. Design: Systematic review and harmonised meta-analysis. Data Sources: Five databases (PubMed, PsycINFO, Embase, Web of Science, Sport Discus) from database inception until July 31st 2018. Eligibility Criteria: Prospective cohort studies assessing physical activity and sedentary time by accelerometry; had data on individual level exposure and outcome (all-cause mortality); and reported effect estimates as hazard ratios (HR), odds ratios (OR) or relative risk (RR) with 95% confidence intervals (95% CI) for all-cause mortality. Data Extraction and Analysis: Guidelines for meta-analyses and systematic reviews for observational studies and PRISMA guidelines were followed. Two authors independently screened all titles and abstracts. One author performed a full-text review and one author extracted the data. Two authors independently assessed the risk of bias. Individual level participant data were harmonised and analysed at study level. Exposure data were categorised by quartiles at study level and study specific associations with all-cause mortality were analysed using Cox proportional hazards regression analyses. Study specific results were thereafter summarised using random-effects meta-analysis. Main Outcome: All-cause mortality Results: Thirty-nine studies were retrieved for full text review; 10 were eligible for inclusion, 3 of these studies were excluded due to harmonisation challenges and 1 study did not participate. Two additional pertinent studies with unpublished mortality data were also included. Thus, individual level data from eight studies (n=36,383; mean age 62.6 years; 72.8% women), with median follow-up time of 5.8 years (range 3.0 to 14.5 years) during which 2,149 (5.9%) died, were analysed. Any physical activity, regardless of intensity, was associated with lower risk of mortality with a non-linear, dose-response. Hazards ratios for mortality were 1.00 (referent), 0.48 (95% confidence interval: 0.43 to 0.54), 0.34 (0.26 to 0.45) and 0.27 (0.23 to 0.32) for increasing quartiles for total physical activity. Corresponding hazards ratios for light-intensity activity were 1.00, 0.60 (0.54 to 0.68), 0.44 (0.38 to 0.51), and 0.38 (0.28 to 0.51); and 1.00, 0.64 (0.55 to 0.74), 0.55 (0.40 to 0.74), and 0.52 (0.43 to 0.61) for moderate-to-vigorous intensity activity. For sedentary time, hazards ratios were 1.00 (referent), 1.28 (1.09 to 1.51), 1.71 (1.36 to 2.15) and 2.63 (1.94 to 3.56). Conclusion: Higher levels of total physical activity, at any intensity, and less sedentary time, are associated with substantially reduced risk for premature mortality with evidence of a non-linear dose-response pattern in middle-aged and older individuals. Systematic Review Registration: PROSPERO 2018 CRD42018091808