title: High platelet count as a link between renal cachexia and cardiovascular mortality in end-stage renal disease patients.
abstract: BACKGROUND
  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).
  
  
  OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Harold Simmons Center for Chronic Disease Research & Epidemiology, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, CA, USA.
authors.forename: Miklos Z
authors.initials: MZ
authors.lastname: Molnar
authors.forename: Elani
authors.initials: E
authors.lastname: Streja
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
authors.forename: Allen R
authors.initials: AR
authors.lastname: Nissenson
authors.forename: Mahesh
authors.initials: M
authors.lastname: Krishnan
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Keith C
authors.initials: KC
authors.lastname: Norris
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.forename: Kamyar
authors.initials: K
authors.lastname: Kalantar-Zadeh
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D000418:Albumins / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000401:mortality*; D002100:Cachexia / Q000097:blood / Q000150:complications*; D002423:Cause of Death; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D003920:Diabetes Mellitus / Q000453:epidemiology; D003956:Dialysis; D004044:Dietary Proteins / Q000008:administration & dosage; D004921:Erythropoietin / Q000008:administration & dosage; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications* / Q000401:mortality; D008297:Male; D044342:Malnutrition / Q000097:blood / Q000150:complications*; D008875:Middle Aged; D010976:Platelet Count; D015995:Prevalence; D013922:Thrombocytosis / Q000097:blood / Q000150:complications* / Q000401:mortality
chemical_list: D000418:Albumins; D004044:Dietary Proteins; D006454:Hemoglobins; D004921:Erythropoietin; D003404:Creatinine