Non-occupational physical activity and risk of 22 cardiovascular disease, cancer, and mortality outcomes: a dose-response meta-analysis of large prospective studies

Objective: To estimate dose-response associations between non-occupational physical activity and multiple chronic disease outcomes in the general adult population. Eligibility criteria: Prospective cohort studies with (a) general population samples >10,000 adults, (b) [≥]3 exposure categories, and (c) risk measures and confidence intervals for all-cause mortality, total cardiovascular disease, coronary heart disease, stroke, heart failure, total cancer, and site-specific cancers (head and neck, myeloid leukemia, myeloma, gastric cardia, lung, liver, endometrium, colon, breast, bladder, rectum, esophagus, prostate, kidney). Information sources: PubMed, Scopus, Web of Science, and reference lists of published studies, searched in February 2019. Data extraction and synthesis: Independent extraction and double-checking of study characteristics, exposure, and outcome assessment by two reviewers for each paper. Primary exposure was non-occupational physical activity volume, harmonized to physical activity energy expenditure in marginal MET-hours per week (mMET-h/week). The current minimum recommendations for physical activity (150 min/week of moderate-to-vigorous physical activity) equate to 8.75 mMET-h/week. Outcomes were risks of mortality, cardiovascular diseases, and cancers. We used restricted cubic splines in random-effects meta-analyses. Potential population impact was quantified using impact fractions. Results: 196 articles were included, covering 94 cohorts. The evidence base was largest for all-cause mortality (50 independent results; 163,415,543 person-years; 811,616 events), and incidence of cardiovascular disease (37 independent results; 28,884,209 person-years; 74,757 events) and cancer (31 independent results; 35,500,867 person-years; 185,870 events). In general, inverse non-linear associations were observed, steeper between 0 and 8.75 mMET-h/week, with smaller marginal reductions in risk above this level to 17.5 mMET-h/week, beyond which additional reductions were small and uncertain. Associations were stronger for all-cause and cardiovascular disease mortality than for cancer mortality. If all insufficiently active individuals had met the recommended physical activity level, 15.7% (95%CI: 13.1 to 18.2%) of all premature deaths would have been averted. Conclusions: Inverse non-linear dose-response associations suggest substantial protection against a range of chronic disease outcomes from small increases in non-occupational physical activity in inactive adults. Review registration: PROSPERO CRD42018095481.