title: Elevated serum free pregnancy-associated plasma protein-A independently predicts mortality in haemodialysis patients but is not associated with recurrent haemodialysis-induced ischaemic myocardial injury.
abstract: OBJECTIVE
  Pregnancy-associated plasma protein-A (PAPP-A) is a putative marker of atheroma instability and ischaemic myocardial stress prior to necrosis. Total PAPP-A (tPAPP-A) levels in acute coronary syndromes predict adverse outcomes. However, free PAPP-A (fPAPP-A) predominates in the circulation. Ischaemic haemodialysis (HD)-induced cardiac injury (myocardial stunning) is common and is associated with markers of myocardial necrosis, inflammation, cardiovascular events and mortality. Coronary plaque instability in pathophysiology of HD-induced myocardial stunning has not been studied. We aimed to investigate the relationship of fPAPP-A with stunning and mortality.
  
  
  METHODS
  130 prevalent patients from two HD centres (Finland and UK) were studied. Pre-HD free, complexed and total PAPP-A were measured by immunoassay. A subset of 62 patients underwent echocardiography to assess HD-induced myocardial stunning. The mean duration of follow-up was 407 ± 98 days.
  
  
  RESULTS
  fPAPP-A was elevated (median: 3.45 mIU/l) and correlated with dialysis vintage (r = 0.391, p < 0.001), cardiac troponin T (cTnT; r = 0.29, p = 0.001) and cardiac troponin I (cTnI; r = 0.22, p = 0.01). PAPP-A was not related to stunning. Dialysis vintage and cTnT independently predicted Ln fPAPP-A (model R = 0.463). fPAPP-A, cTnT and age independently predicted death (Nagelkerke R(2) = 0.362).
  
  
  CONCLUSIONS
  fPAPP-A, a novel predictor of HD-related mortality, demonstrates better prognostic power than tPAPP-A. Coronary plaque instability may contribute to sub-lethal myocardial injury, but may not be critical in pathogenesis of HD-induced ischaemic cardiac injury.
authors.affiliation: Department of Renal Medicine, Royal Derby Hospital, Derby, UK.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Jefferies
authors.forename: Risto
authors.initials: R
authors.lastname: Tertti
authors.forename: Saara
authors.initials: S
authors.lastname: Wittfooth
authors.forename: James O
authors.initials: JO
authors.lastname: Burton
authors.forename: Kaj
authors.initials: K
authors.lastname: Metsärinne
authors.forename: Kim
authors.initials: K
authors.lastname: Pettersson
authors.forename: Christopher W
authors.initials: CW
authors.lastname: McIntyre
mesh_terms: D000368:Aged; D015415:Biomarkers; D015331:Cohort Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D006334:Heart Function Tests; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000209:etiology*; D017682:Myocardial Stunning / Q000209:etiology / Q000503:physiopathology; D011237:Predictive Value of Tests; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis / Q000378:metabolism*; D006435:Renal Dialysis / Q000009:adverse effects* / Q000401:mortality*; D019209:Troponin C / Q000097:blood; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D019209:Troponin C; D011266:Pregnancy-Associated Plasma Protein-A