Pregnancy-associated plasma protein A associates with cardiovascular events in diabetic hemodialysis patients

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 4th 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 4th 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. (C) 2014 The Authors. Published by Elsevier Ireland Ltd.