ABSTRACT: Background:Obesity is 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, and also whether systemic inflammation independently affects HRQOL. We conducted an exploratory analysis to investigate the relationships between obesity, systemic inflammation and indices of HRQOL, using NHANES survey data. Methods:Data for the variables of interest were available for 6325 adults (aged 20-75 years, BMI?>?18.5 kg/m2). 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. Data was subjected to multiple imputation in order to mitigate information loss from survey non-response. Both main effects and interaction effects were analyzed to evaluate possible mediation or moderation effects. Model robustness was ascertained via sensitivity analysis. Averaged results from the imputed datasets were reported in as odds ratios (OR) and confidence intervals (CI). Results:Obesity 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 appears to mediate the association between obesity and physical unhealthy days. Clinically raised inflammation is an independent determinant of physical and mental unhealthy days. Importantly, elevated (but sub-clinical) inflammation is also negatively associated with physical healthy days, and may warrant more attention from a population health perspective than currently appreciated.
