MAJOR ADIPOSE TISSUE CYTOKINES LEPTIN AND ADIPONECTIN INTERACT WITH CENTRAL OBESITY IN EXPLAINING THE VARIABILITY IN ALL-CAUSE AND CARDIOVASCULAR DEATH IN A HIGH RISK POPULATION: PP.9.345:

The relationship between the adipose tissue cytokines leptin and adiponectin and major clinical outcomes like survival and cardiovascular events is still undefined. We made detailed analyses of these associations in a high risk population like End Stage Renal Disease (ESRD). Leptin and Adiponectin are much increased in a substantial proportion of ESRD patients. Therefore, ESRD constitutes a natural model for testing the relationship of high levels of these cytokines and clinical outcomes. Since abdominal fat is an important modifier of the effect of various risk factors for death and cardiovascular complications, we specifically tested the hypothesis waist circumference (WC) modifies the link between these cytokines and overall and cardiovascular (CV) death in a cohort of 537 hemodialysis patients. Leptin and adiponectin were inversely related each other and robustly associated with waist circumference (all P < 0.001). During the follow-up period (average: 29 months, range 1–47 months) 182 patients died, 113 of them of CV causes. In multivariable Cox models including traditional and non-traditional risk factors there were strong interactions between serum leptin and WC in relationship to both, all-cause (P < 0.001) and CV death (P = 0.002). Accordingly, a fixed excess in serum leptin signalled a gradually lower risk for all-cause and CV mortality in patients with waist circumference < 110 cm but an opposite effect in those with WC above this threshold. An interaction between adiponectin and WC for all-cause (P = 0.01) and CV mortality (P = 0.01) emerged only in models excluding the leptin-WC interaction, suggesting that these adipokines share a common pathway conducive to adverse clinical events in ESRD patients. The predictive values of Leptin and Adiponectin for all-cause and CV death in ESRD patients appear critically dependent on WC. Overall these findings generate the hypothesis that intervention studies in ESRD patients with abdominal obesity and deranged adipokines levels may translate into better clinical outcomes.