Analysis methods to determine the optimal combination of volume and intensity of objectively measured physical activity (PA) with prospective outcomes are limited. Participants in UK Biobank were recruited in the UK between 2006 and 2010. We linked the questionnaire and accelerometer with all-cause mortality data from the NHS Information Centre and NHS Central Register up to April 2021. We developed a novel method, extending the penalized spline model of Augustin et al. to a smooth additive Cox model for survival data, and estimated the prospective relationship between intensity distribution and all-cause mortality, adjusting for the overall volume of PA. We followed 84,166 men and women (aged 40-69) for an average of 6.4 years (range 5.3-7.9), with an observed mortality rate of 22.2 deaths per 1000. Survival rates differed by PA volume quartile, with poorer outcomes for the lowest PA volumes. Participants with more sedentary to light intensity PA (<100 milligravities (mg)) and/or less vigorous intensity PA (>250 mg) than average for a given volume of PA, had higher mortality rates than vice versa. Approximate hazard ratios were 0.83 (95% credible interval [CI]: 0.79, 0.88) for an average-risk profile compared to a high-risk profile and 0.80 (95% CI: 0.74, 0.87) for a low-risk profile compared to an average-risk profile. A high- versus low-risk profile has the equivalent of 15 min more slow walking, but 10 min less moderate walking. At low PA volumes, increasing overall volume suggests the most benefit in reducing all-cause mortality risk. However, at higher overall volumes, substituting lighter with more vigorous intensity activity suggests greater benefit.
Keywords: all-cause mortality; methods development; physical activity intensity distribution; prospective cohort study.