Comorbid conditions and the transition among states of hip osteoarthritis and symptoms in a community-based longitudinal study: a multi-state model approach

Abstract

Purpose: Conditions such as obesity, diabetes mellitus (DM), and cardiovascular disease (CVD) are associated with osteoarthritis (OA). However, it is unknown how these associations translate to progression among states of OA. We sought to examine the association of obesity, DM, and CVD, overall, with characteristics of hip OA. Methods: A longitudinal analysis of 3857 individuals with complete data was performed using data from baseline and up to three follow-up periods in the Johnston County Osteoarthritis Project (JoCoOA), a longitudinal community-based study of African American and Caucasian men aged 45 years or older and women over 50 with approximately 18 years of follow-up. Radiographic hip OA (rHOA) was defined by radiographic hip evidence of OA in at least one hip (Kellgren-Lawrence grade ≥ 2. Hip symptoms were defined by self-reported pain, aching, or stiffness on most days, and symptomatic rHOA (sxHOA) was defined by rHOA and hip symptoms in the same hip. rHOA progression states of interest included: 1) no rHOA or hip symptoms, 2) asymptomatic rHOA, 3) hip symptoms only, 4) sxHOA, and 5) death—with transitions of interest indicated by arrows in Fig. 1. Vital status was ascertained through National Death Index records to determine death date and allow for modeling of death as an absorbing state. Person-years of follow-up were accrued from baseline to death or censored at loss to follow-up or December 31, 2015. A Markov multistate model (MSM), based on the theory of stochastic processes, was conducted to model the progression of rHOA states over time and allow for the analysis of states observed at arbitrary times (i.e., interval censored events or panel data). These models rely on piecewise-constant hazard approximation and were fit using the msm R package. Obesity (body mass index ≥ 30 kg/m2), self-reported DM, and self-reported CVD were included as time-dependent comorbid conditions of interest. This Markov MSM was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) to determine associations between each comorbid condition and rHOA state transitions. Additionally, the model adjusted for baseline demographics including age, sex, race, education, enrollment cohort, birth year, as well as time-dependent hip injury history. Results: At baseline, the sample consisted of 33% African Americans, 39% men, with a mean (SD) age of 62.2 (9.8) years, and 37% with less than a 12 year education level. Forty percent were obese at baseline increasing up to 50% during follow-up; 14% had DM at baseline increasing up to 28% during follow-up; and 22% had CVD at baseline increasing up to 48% during follow-up. At baseline, 45% had no rHOA or hip symptoms, 25% had hip symptoms only, 19% had asymptomatic rHOA, and 11% had sxHOA. Table 1 shows frequencies for observed transitions among these four rHOA states as well as death. Table 2 shows HR and 95% CI, with significant associations indicated in bold. CVD decreased the chance of improving from a state of hip symptoms only to a state of neither rHOA nor symptoms (3–>1) and, although not significantly, increased the risk of worsening from a state of neither rHOA nor symptoms to a state of asymptomatic rHOA (1–>2). Obesity increased the risk of worsening from a state of neither rHOA nor symptoms to a state of hip symptoms only (1–>3). DM was not associated overall with any modeled transitions. Conclusions: Results suggest that there are a few single impacts between conditions of obesity and CVD, in particular, with specific hip OA and symptom state transitions, independent of relevant demographic and clinical factors. Further analysis should consider whether these conditions in combination are associated similarly or additionally with transitions of hip OA and symptoms.