Knee osteoarthritis and time-to all-cause mortality in six community-based cohorts: an international meta-analysis of individual participant-level data
K.M. Leyland, Lucy Gates, María T. Sánchez-Santos, Michael C. Nevitt, David T. Felson, Graeme Jones, Joanne M. Jordan, Andrew Judge, Daniel Prieto‐Alhambra, Noriko Yoshimura, Julia L. Newton, Leigh F. Callahan, Cyrus Cooper, Mark E. Batt, Jianhao Lin, Qiang Liu, Rebecca J. Cleveland, Gary S. Collins, Nigel Arden, Lyn March, Gillian Hawker, Philip G. Conaghan, Virginia B. Kraus, Ali Guermazi, David J. Hunter, Jeffrey N. Katz, T.E. McAlindon, Tuhina Neogi, Lee S. Simon, Marita Cross, Lauren King
Abstract
BACKGROUND: Osteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population. METHODS: Seven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung-Knapp modification for random-effects meta-analysis. FINDINGS: 10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA. DISCUSSION: Participants with POA or PROA had a 35-37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality. FUNDING: Versus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International.