High platelet count as a link between renal cachexia and cardiovascular mortality in end-stage renal disease patients

Abstract

It is not clear why cardiac or renal cachexia in chronic diseases is associated with poor cardiovascular outcomes. Platelet reactivity predisposes to thromboembolic events in the setting of atherosclerotic cardiovascular disease, which is often present in patients with end-stage renal disease (ESRD). We hypothesized that ESRD patients with relative thrombocytosis (platelet count >300 × 10(3)/μL) have a higher mortality rate and that this association may be related to malnutrition-inflammation cachexia syndrome (MICS). We examined the associations of 3-mo-averaged platelet counts with markers of MICS and 6-y all-cause and cardiovascular mortality (2001-2007) in a cohort of 40,797 patients who were receiving maintenance hemodialysis. The patients comprised 46% women and 34% African Americans, and 46% of the patients had diabetes. The 3-mo-averaged platelet count was 229 ± 78 × 10(3)/μL. In unadjusted and case-mix adjusted models, lower values of albumin, creatinine, protein intake, hemoglobin, and dialysis dose and a higher erythropoietin dose were associated with a higher platelet count. Compared with patients with a platelet count of between 150 and 200 × 10(3)/μL (reference), the all-cause (and cardiovascular) mortality rate with platelet counts between 300 and <350, between 350 and <400, and ≥400 ×10(3)/μL were 6% (and 7%), 17% (and 15%), and 24% (and 25%) higher (P < 0.05), respectively. The associations persisted after control for case-mix adjustment, but adjustment for MICS abolished them. Relative thrombocytosis is associated with a worse MICS profile, a lower dialysis dose, and higher all-cause and cardiovascular disease death risk in hemodialysis patients; and its all-cause and cardiovascular mortality predictability is accounted for by MICS. The role of platelet activation in cachexia-associated mortality warrants additional studies.