Abstract
BACKGROUND: This study aims to evaluate the mediation effect of dyslipidemia induced inflammation on the causal associations between obesity and Osteoarthritis (OA). METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey (1999-2010). The association between general and abdominal obesity (exposure), OA (outcome) and mediators (total cholesterol, high-density lipoprotein, and C-reactive protein) was assessed using multivariate linear and logistic regression models and mediation analysis. RESULTS: A total of 23,308 participants were enrolled in this study, and 2,180 were diagnosed with OA. Participants with obesity were more likely to have OA (general obesity: OR = 2.508, 95%CI: 1.602, 4.197, P < 0.001; abdominal obesity: OR = 3.814, 95%CI: 3.242, 4.509, P < 0.001) than those without the obesity. High quantile of total cholesterol (OR:1.399; 95%CI:1.235, 1.257; P < 0.001), high-density lipoprotein (OR:1.644; 95%CI:1.443, 1.874; P < 0.001) and C-reactive protein (OR:1.952; 95%CI:1.707, 2.237; P < 0.001) increased the risk of OA when compared to lowest quartile. In the linear regression, the betas varied from 0.668 (95%CI: 0.635, 0.741; P < 0.001) to 0.693 (95%CI: 0.674, 0.712; P < 0.001), suggesting that individual with obesity had higher C-reactive protein levels. Additionally, total cholesterol and high-density lipoprotein were associated with C-reactive protein. Mediation analyses showed that the causal association of obesity with OA risk was mediated by high-density lipoprotein and C-reactive protein, with the mediation proportion ranging from 17.216 to 45.058%. Moreover, high-density lipoprotein to C-reactive protein path acting as serial mediators in the associations between obesity and OA (general obesity: β = 0.012; 95%CI: 0.009-0.014; abdominal obesity: β = 0.011; 95%CI: 0.008-0.014). CONCLUSION: The association between obesity and OA is partially mediated by systemic inflammation caused by dyslipidemia. Our study suggested anti-lipid therapy may be positive for obese individuals with OA.