Marta Kalousová1, Tomáš Zima2, Vera Krane3, Winfried März4, Christoph Wanner5, Vladimír Tesař6, Christiane Drechsler7. 1. 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. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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.
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.
RCT Entities:
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 diabeticpatients undergoing dialysis. METHODS:PAPP-A was measured in 1098 diabetic hemodialysispatients, 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.