Relation of Multiple Low-Risk Lifestyle Behaviors With Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies

Introduction: The association of combined low-risk lifestyle behaviors (LRLBs) with cardiovascular disease (CVD) and all-cause mortality has not been systematically quantified. Objective: We undertook a systematic review and dose-response meta-analysis to assess the association of combined LRLBs with CVD and all-cause mortality. Methods: MEDLINE, EMBASE and Cochrane were searched up to December 29, 2021. Prospective cohort studies reporting the association between a minimum of 3 combined LRLBs (including healthy diet) with CVD, coronary heart disease (CHD) and stroke incidence and mortality were included. Independent reviewers extracted data and assessed study quality. Highest vs. lowest LRLB score was pooled using random effects. Heterogeneity was assessed (Cochran Q) and quantified (I 2 ). Global dose response meta-analysis (DRM) for maximum adherence was estimated using one-stage linear mixed model. The certainty of the evidence was assessed using GRADE. Results: 116 cohort comparisons (n=9,775,191) involving 382,922 cases were included. Comparing highest with lowest adherence LRLBs were associated with lower risk of CHD incidence (RR, 0.29 [95% CI, 0.21, 0.42]), stroke incidence (0.56 [0.50, 0.62]), CVD incidence (0.47 [0.37, 0.58]), CHD mortality (0.32 [0.25, 0.41]), stroke mortality (0.37 [0.30, 0.46]), CVD mortality (0.41 [0.34, 0.49]) and all-cause mortality (0.46 [0.41 to 0.52]). DRM analysis showed a linear association between LRLBs and all outcomes reaching a global DRM between 59-76% protection. LRLBs were defined with variable ranges as a healthy body weight (body mass index <30kg/m 2 ), healthy diet (healthy diet score >median), regular physical activity (1/week to >30 minutes/day), smoking cessation (never smoked or smoking cessation), light alcohol intake (≤30g/day) and adequate sleep (5.5-9 hours). The certainty of the evidence was graded as moderate to high owing to downgrades for inconsistency and/or upgrades for a large magnitude of effect and significant dose-response gradient. Conclusions: Pooled analyses show that the combination of LRLBs was associated with a substantial lower risk of CVD outcomes and all-cause mortality. The available evidence provides a very good indication of the benefit of combined LRLBs.