title: Pregnancy-associated plasma protein A associates with cardiovascular events in diabetic hemodialysis patients.
abstract: OBJECTIVE
  Pregnancy-associated plasma protein A (PAPP-A) has prognostic impact in pregnancy and acute coronary syndrome. Patients with chronic kidney disease have an excessive cardiovascular risk. In an effort to identify novel risk factors for cardiovascular disease, we investigated the relationship of PAPP-A with specific outcomes in diabetic patients undergoing dialysis.
  
  
  METHODS
  PAPP-A was measured in 1098 diabetic hemodialysis patients, who participated in the German Diabetes and Dialysis Study and followed-up for a median of 4 years. By Cox regression analysis, we assessed the association of baseline levels of PAPP-A with all-cause mortality, combined cardiovascular events and the specific outcomes of sudden death, stroke, myocardial infarction and infectious mortality.
  
  
  RESULTS
  Patients had a mean age of 66 ± 8 years (54% male) and median PAPP-A concentration of 17 mIU/L (IQR 13.4-20.9 mIU/L). Per standard deviation increase in PAPP-A the adjusted risk of sudden cardiac death increased by 23% (HR 1.23, 95%CI 1.12-1.36). Categorical analyses showed that the patients in the 4(th) PAPP-A quartile had an adjusted 2.6 fold increased risk of sudden death and 2.8 fold increased risk of stroke as compared to the patients in the 1st quartile. Similarly, the risk of combined cardiovascular events was significantly elevated by the factor 1.5 in patients of the 4(th) quartile. Additionally, PAPP-A levels were associated with infectious deaths and all-cause mortality.
  
  
  CONCLUSIONS
  PAPP-A is associated with sudden death, stroke and infectious complications in diabetic dialysis patients. PAPP-A may be useful for risk assessment and monitoring in populations at high risk of cardiovascular events.
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic. Electronic address: marta.kalousova@lf1.cuni.cz.
authors.forename: Marta
authors.initials: M
authors.lastname: Kalousová
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic. Electronic address: zimatom@cesnet.cz.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Zima
authors.affiliation: Division of Nephrology, Department of Medicine 1, University Hospital Würzburg, Würzburg, Germany; Comprehensive Heart Failure Centre, University of Würzburg, Würzburg, Germany. Electronic address: krane_v@medizin.uni-wuerzburg.de.
authors.forename: Vera
authors.initials: V
authors.lastname: Krane
authors.affiliation: Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Mannheim Medical Faculty, Heidelberg University, Mannheim, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; Synlab Academy, Synlab Services GmbH, Mannheim, Germany. Electronic address: winfried.maerz@synlab.com.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Division of Nephrology, Department of Medicine 1, University Hospital Würzburg, Würzburg, Germany; Comprehensive Heart Failure Centre, University of Würzburg, Würzburg, Germany. Electronic address: wanner_c@medizin.uni-wuerzburg.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.affiliation: Department of Nephrology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic. Electronic address: vladimir.tesar@lf1.cuni.cz.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Tesař
authors.affiliation: Division of Nephrology, Department of Medicine 1, University Hospital Würzburg, Würzburg, Germany; Comprehensive Heart Failure Centre, University of Würzburg, Würzburg, Germany; Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany. Electronic address: drechsler_c@medizin.uni-wuerzburg.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Drechsler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002423:Cause of Death; D015897:Comorbidity; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D048909:Diabetes Complications / Q000453:epidemiology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000453:epidemiology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007239:Infections / Q000401:mortality; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000453:epidemiology / Q000628:therapy; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009203:Myocardial Infarction / Q000453:epidemiology; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use; D006435:Renal Dialysis; D018570:Risk Assessment; D012907:Smoking / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology; D055815:Young Adult
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D000069059:Atorvastatin; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human
keywords: Atherosclerosis; Cardiovascular disease; Diabetes mellitus; Stroke; Sudden death