BACKGROUND: Healthy lifestyle is associated with reduced all-cause mortality, but it is not known whether this association persists for individuals with high medication burden. We examined the association between healthy lifestyle behaviors and all-cause mortality across different degrees of polypharmacy.

METHODS: This was a secondary analysis of 20,417 adults aged ≥45 years from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study. The primary exposure was healthy lifestyle (adherence to Mediterranean diet, physical activity, smoking abstinence, sedentary behavior avoidance, and composite healthy behavior score [HBS]). The primary outcome was all-cause mortality. Strata of medication burden were based on the number of medications taken (no polypharmacy: 0-4, polypharmacy: 5-9, hyperpolypharmacy: ≥10). We used Cox proportional hazards regression models to examine the association between healthy lifestyle behaviors and mortality within each medication burden stratum and examined for interactions with age.

RESULTS: The healthiest category of each lifestyle behavior, except sedentary behavior avoidance among the hyperpolypharmacy group, was associated with lower all-cause mortality (hazard ratio [HR]) regardless of medication burden: Mediterranean diet (no polypharmacy: HR 0.77, polypharmacy: HR 0.78, hyperpolypharmacy: HR 0.85), physical activity (no polypharmacy: HR 0.87, polypharmacy: HR 0.82, hyperpolypharmacy: HR 0.79), smoking abstinence (no polypharmacy: HR 0.40, polypharmacy: HR 0.45, hyperpolypharmacy: HR 0.52), and sedentary behavior avoidance (no polypharmacy: HR 0.88, polypharmacy: HR 0.86, hyperpolypharmacy: HR 0.95). Higher HBS was inversely associated with all-cause mortality within each medication burden stratum (no polypharmacy: HR 0.52, polypharmacy: HR 0.55, hyperpolypharmacy: HR 0.69). Although there was an interaction with age among those with no polypharmacy and those with polypharmacy, point estimates for HBS followed a graded pattern whereby higher HBS was incrementally associated with improved mortality across all age strata.

CONCLUSION: Greater adherence to a healthy lifestyle was associated with lower all-cause mortality irrespective of medication burden and age.