Intensity-specific leisure time-physical activity and all-cause, cardiovascular, and cancer mortality in 3.36 million adults from 17 countries: a systematic review, meta-analysis, and individual participant data pooled analysis

Background: Studies examining the associations of intensity-specific leisure time physical activity duration with all-cause, cardiovascular disease (CVD), and cancer mortality are scarce and no quantitative or dose-response meta-analysis has been published. Objective: We examined the associations of moderate, vigorous, and moderate to vigorous leisure time physical activity duration with all-cause, CVD, and cancer mortality, using aggregate and individual participant data. Methods: We performed a systematic review and meta-analysis of both published and unpublished cohort studies that included data on intensity-specific leisure time physical activity. Hazard ratios (HR) were calculated by comparing high versus low levels of physical activity. We also harmonized and pooled individual participant data from unpublished large cohorts to assess dose-response associations with the same three mortality outcomes, as retrieved from National Death Registries. Results: A total of 3.36 million participants across 25 cohorts and 17 countries, corresponding to 247,463 all-cause, 70,204 CVD, and 76,294 cancer deaths were included in our aggregate meta-analysis. Compared to low physical activity, the association of high moderate intensity leisure time physical activity with mortality ranged from an HR of 0.84 (95% CI= 0.79, 0.89) for all-cause mortality to 0.90 (0.86, 0.95) for cancer mortality; and vigorous intensity from 0.86 (0.79, 0.93) for all-cause mortality to 0.88 (0.83, 0.91) for cancer mortality. Our pooled individual participant data analysis included 967,184 participants with an average follow-up time of 12.2 (SD= 4.7) years and 60,206 all-cause, 11,525 CVD, and 23,740 cancer deaths. The dose-response analysis showed a general L-shaped association across each outcome. For all-cause mortality, compared to the reference group with no leisure time activity, the minimal and optimal doses of vigorous intensity were 60 mins/week (0.86 [0.84, 0.89]) and 200 mins/week (0.69 [0.67, 0.71]), respectively. For moderate intensity, the corresponding doses were 100 mins/week (0.88 [0.86, 0.90]) and 340 mins/week (0.77 [0.75, 0.79]). Conclusions: Our meta-analysis shows distinct differential associations of moderate and vigorous physical activity with all-cause, cardiovascular, and cancer mortality risk. Improvements in leisure time physical activity approximately equivalent to 60 mins/week of vigorous or 100 mins/week of moderate activity, may be linked with measurable health benefits. Our findings, synthesized uniquely through aggregated and pooled individual participant meta-analyses offer novel evidence to guide decisions on contents of leisure time physical activity focused interventions and preventive guidelines.