Abstract

Background There is increasing evidence that it is the impact of osteoarthritis rather than the osteoarthritis itself that explains an excess risk of mortality. This indicates that potentially modifiable targets may reduce mortality for those with osteoarthritis. Mediation analysis can be used to investigate pathways, although this has rarely been undertaken using survival analysis due to the challenge of accounting for time. The study uses a novel approach to examine mediation using path analysis with Cox proportional hazard modelling (survival analysis). Objectives The objectives of this study were to identify potential mechanisms of the impact of osteoarthritis on mortality and examine the role of modifiable targets (anxiety, depression, insomnia and walking frequency) for health professionals in rheumatology (HPRs). Methods A population-based prospective cohort study was conducted using data from the North Staffordshire Osteoarthritis Project (NorStOP), in which primary care medical record data was linked to self-report information collected by questionnaire in adults aged 50 years and over (n=8066). Individuals were defined as having osteoarthritis if they had consulted general practice for osteoarthritis, identified by Read codes in the primary care medical record, and indicated moderate to severe pain interference in daily life in the Medical Outcomes Short Form 36 at baseline (2002). A Cox proportional hazards analysis was performed to determine the total effect (TE) of osteoarthritis on mortality, both with adjustment for confounding variables (age, sex, education, occupation, smoking status, ischaemic heart disease, chronic obstructive pulmonary disease, non-steroidal anti-inflammatories, obesity, cognitive impairment). Within the Cox model, path analysis was used to decompose the TE to assess the indirect (IE) and direct effects (DE) for each of four potential mediators (anxiety, depression, insomnia, walking frequency; all measured by questionnaire) with adjustment for confounders. Results are expressed as adjusted hazard ratios (aHR); bootstrap resampling was used to generate 95% confidence intervals (95% CIs). Results Mean age of participants was 65.2 (SD 9.8) years and 51.6% were female. 2396 (29.7%) had osteoarthritis. Participants were followed up over 10 years during which time 1188 (14.7%) died. The rate of mortality was greater in those with osteoarthritis (52 deaths per 1000 person years) compared to those without (38 deaths per 1000 person years). Osteoarthritis was significantly associated with mortality (aHR 1.14; 1.00, 1.28). The relationship between osteoarthritis and mortality was mediated by walking frequency, depression and insomnia (anxiety did not mediate the relationship (IE HR 1.00; 0.98, 1.02)). The strongest mediator was walking frequency (TE 1.14; 1.00, 1.29: DE 1.04; 0.91, 1.18: IE 1.08; 1.06, 1.11), followed by depression (IE 1.06; 1.03, 1.08) and insomnia (IE 1.01; 1.00, 1.03). Conclusion This is the first study to examine mediation and highlights the importance of potentially modifiable targets for HPRs to reduce mortality in older adults with osteoarthritis. Encouraging people to maintain levels of physical activity at a population level and targeting a reduction in physical limitation in clinical practice to allow this, is important. Disclosure of Interests None declared

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