Effect of increased leptin and C-reactive protein levels on mortality: Results from the national health and nutrition examination survey

Objective: Leptin and C-reactive protein (CRP) have each been linked to adverse cardiovascular events, and prior cross-sectional research suggests that increased levels of both biomarkers pose an even greater risk. The effect of increased levels of both leptin and CRP on mortality has not, however, been previously assessed. Methods: We used data from the third National Health and Nutrition Examination Survey (NHANES III) to estimate the mortality effect of high leptin and high CRP levels. Outcomes were compared with the use of inverse-probability-weighting adjustment. Among 6259 participants included in the analysis, 766 were in their sex-specific, population-weighted highest quartiles of both leptin and CRP. Median follow-up time was 14.3 years. Results: There was no significant difference in adjusted all-cause mortality between the groups (risk ratio 1.22, 95% confidence interval [CI], 0.97-1.54). Similar results were noted with the use of several different analytic methods and in many subgroups, though high leptin and CRP levels may increase all-cause mortality in males (hazard ratio, 1.80, 95% CI, 1.32-2.46; P for interaction, 0.011). A significant difference in cardiovascular mortality was also noted (risk ratio, 1.54, 95% CI, 1.08-2.18), though that finding was not confirmed in all sensitivity analyses. Conclusions: In this observational study, no significant difference in overall all-cause mortality rates in those with high leptin and high CRP levels was found, though high leptin and CRP levels appear associated with increased mortality in males. High leptin and CRP levels also likely increase risk for cardiovascular death.