Associations of Healthy Lifestyles with All-Cause Mortality Among Individuals with Osteoarthritis: Results from UK Biobank and US NHANES

OBJECTIVE: To investigate the association of both individual and combined healthy lifestyle factors with the risk of all-cause mortality among patients with osteoarthritis (OA). DESIGN: Prospective population-based cohort study. SETTING: UK biobank and US National Health and Nutrition Examination Survey (US NHANES, 2007-2018) PARTICIPANTS: 104, 142 UK participants with OA aged 39-72 years and 3, 472 US participants with OA aged 20-80 years. EXPOSURES: Individual healthy lifestyle factors and a combined healthy lifestyle score were constructed from body mass index (BMI) and self-reported information on diet, sleep duration, physical activity, sedentary time, social connection, smoking and alcohol drinking. MAIN OUTCOME MEASURES: All-cause mortality was the primary outcome in both studies. Secondary outcomes included cause-specific mortalities (cardiovascular, cancer, digestive and respiratory). Hazard ratios were adjusted for age, sex, economic situation, race, education and employment (UK biobank only). RESULTS: UK Biobank documented 9,914 deaths during a median follow-up of 12.7 years, and US NHANES documented 463 deaths during a mean follow-up of 6.01 years. For all-cause mortality using restricted cubic spline graph (RCS) models, sleep duration had a U-shaped (with a nadir at 7 hours/day), moderate physical activity (MPA) had an L-shaped (with a turning point at 550 minutes/week), while BMI, vigorous physical activity (VPA) and sedentary time had J-shaped (with turning points at 28 kg/m2, 240 minutes/week and 5 hours/day, respectively) associations in the UK biobank. Similar results were observed in US NHANES. In multivariable Cox models, each healthy lifestyle factor was significantly associated with all-cause mortality (hazard ratio [HRs] range 0.49 to 0.84 for UK biobank, and 0.26 to 0.73 for US NHANES), and HRs (95% CI) for associations with combined healthy lifestyle score (scoring 6-8 vs. 0-2) were 0.38 (0.35, 0.41) in UK biobank and healthy lifestyle score (scoring 5-7 vs. 0-1) were 0.20 (0.13, 0.31 ) in US NHANES for all-cause mortality. The results for cause-specific mortality were largely similar and consistent across two cohorts. CONCLUSIONS: The nonlinear relationships suggested patients with OA had the lowest risk of all-cause mortality when BMI was 28 kg/m2, sleep was 7 hours/day, VPA was 240 minutes/week, sedentary time was less than 5 hours/day, MPA was more than 550 minutes/week. The newly constructed healthy lifestyle score for OA population was associated with a significantly lower risk of all-cause mortality. ### Competing Interest Statement All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: Hunter DJ Provides consulting advice on scientific advisory boards for Pfizer, Lilly, TLCBio, Novartis. QY works in a unit that receives core funding from the University of Bristol and UK Medical Research Council (MM\_UU\_00011/6). ### Funding Statement The present study was supported by the National Natural Science Foundation of China (32000925), Guangzhou Science and Technology Program (202002030481) and Clinical Research Startup Program of Southern Medical University (LC2019ZD015). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: We used data from the UK Biobank (application number 67654) and US NHANES (2007-2018). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The phenotypic UK Biobank data are available on application to the UK Biobank (www.ukbiobank.ac.uk/)