European Heart Journal Advance Access published online on October 21, 2009
European Heart Journal, doi:10.1093/eurheartj/ehp429
Pregnancy-associated plasma protein-A is an independent short-time predictor of mortality in patients on maintenance haemodialysis
1 Renal Division, Stadtspital Waid, Tièchestrasse 99 CH-8037 Zurich, Switzerland
2 Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zürich, Zurich, Switzerland
3 Renal Division, Kantonsspital Baden, Baden, Switzerland
4 Renal Division, Kantonsspital Winterthur, Winterthur, Switzerland
5 Renal Division, Kantonsspital Liestal, Liestal, Switzerland
6 Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
7 Renal Division, Kantonsspital Schaffhausen, Schaffhausen, Switzerland
8 Renal Division Regionalspital Lachen, Lachen, Switzerland
9 Department of Psychosocial Medicine, University Hospital Zurich and Stadtspital Waid, Zurich, Switzerland
Received 28 May 2009; revised 25 August 2009; accepted 21 September 2009 * Corresponding author. Tel: +41 44 366 21 55, Fax: +41 44 366 20 76, Email: patrice.ambuehl{at}waid.zuerich.ch
Aims: Mortality of maintenance haemodialysis (HD) patients is very high due to polymorbidity, mostly from metabolic and cardiovascular disease. In order to identify patients with high risk for life-threatening complications, reliable prognostic markers would be helpful. Pregnancy-associated plasma protein-A (PAPP-A) has been shown to predict cardiovascular events and death in patients with stable coronary artery disease as well as in acute coronary syndrome in patients with normal renal function. It was the aim of this study to evaluate PAPP-A as a marker for death in patients on maintenance HD.
Methods and results: PAPP-A serum levels were measured in 170 patients participating in the monitor! trial, a prospective dynamic dialysis cohort multicenter study in Switzerland. Patients were followed up for a median time of 17 months after measuring PAPP-A, and evaluated for death of any cause. Survivors and non-survivors were compared with regard to baseline PAPP-A concentrations. A multivariate logistic regression analysis for death was performed including PAPP-A, age, sex, number of comorbidities, dialysis vintage, Kt/V, IL-6, C-reactive protein, parathyroid hormone (PTH), Ca x PO4 product, and total serum cholesterol. A cut-off value for PAPP-A was calculated for discrimination between patients with low and high mortality risk, respectively. A total of 23 deaths occurred during follow-up, equalling an incidence rate of 0.1. Baseline median PAPP-A levels were 40% higher in non-survivors vs. survivors (P = 0.023). In a multivariate analysis, only PAPP-A, age, and Ca x PO4 product were independent predictors of mortality. A cut-off value of 24 mIU/L discriminates significantly (P = 0.015) between patients at low or high risk for death with a negative predictive value of 91%.
Conclusion: PAPP-A is a novel and independent short-time predictor of mortality in a maintenance HD population. The pathogenetic relevance of PAPP-A, particularly in the development of cardiovascular disease, remains to be further elucidated.
Key Words: Pregnancy associated protein A (PAPP-A) • Chronic renal failure • Haemodialysis • Cardio-renal syndrome • Cardiovascular mortality • Prognosis