Systemic Inflammation Mediates the Relationship between Obesity and Health Related Quality of Life

Background At the population level, obesity has been reported to be positively associated with low-level chronic inflammation, and negatively associated with several indices of health-related quality of life (HRQOL). It is however not clear if obesity-associated inflammation is partly responsible for the observed negative associations between obesity and HRQOL. The present study investigates this question by testing the hypothesis that systemic inflammation is a mediator of the observed association between obesity and a specific HRQOL index called “healthy days”, as measured via a subset of the CDC HRQOL-4 questionnaire.

Methods Demographic, body mass index (BMI), C-reactive protein (CRP), inflammatory disease status, medication use, smoking, and HRQOL data were obtained from NHANES (2005-2008) and analyzed using sampling-weighted generalized linear models. Both main effects and interaction effects were analyzed to evaluate possible mediator-outcome confounding. Model robustness was tested via sensitivity analysis. Prior to model development, data was subjected to multiple imputation in order to mitigate information loss from survey non-response. Averaged results from the imputed datasets were reported in the form of odds ratios (OR) and confidence intervals (CI).

Results Obesity (BMI >30kg/m²) was positively associated with poor physical healthy days (OR: 1.59, 95% CI: 1.15-2.21) in unadjusted models. ‘Elevated’ and ‘clinically raised’ levels of the inflammation marker CRP were also positively associated with poor physical healthy days (OR= 1.61, 95% CI: 1.23-2.12, and OR= 2.45, 95% CI: 1.84-3.26, respectively); additionally ‘clinically raised’ CRP was positively associated with mental unhealthy days (OR= 1.66, 95% CI: 1.26-2.19). The association between obesity and physical HRQOL was rendered non-significant in models including CRP. Association between ‘elevated’ and ‘clinically raised’ CRP and physical unhealthy days remained significant even after adjustment for obesity or inflammation-modulating covariates (OR= 1.36, 95% CI :1.02-1.82, and OR= 1.75, 95% CI: 1.21-2.54, respectively).

Conclusions Systemic inflammation is a significant mediator of the association between obesity and physical unhealthy days. and is also an independent determinant of physical and mental unhealthy days. Importantly, elevated inflammation below the clinical threshold is also negatively associated with physical healthy days and may warrant more attention from a population health perspective than currently appreciated.