Pregnancy-associated plasma protein A and mortality in haemodialysis

Abstract

Elevated pregnancy-associated plasma protein A (PAPP-A) levels are associated with increased risk of death in ischaemic heart disease as well as in haemodialysis patients. Previous research indicates that the prognostic value of PAPP-A may be stronger in patients with concomitant diabetes mellitus or signs of inflammation. We studied the association between PAPP-A and outcomes in prevalent haemodialysis patients and hypothesized that diabetes mellitus and inflammation status act as effect modifiers. Circulating PAPP-A levels were quantified using ELISA. Cox proportional hazards and quantile regression models were used for associations between PAPP-A and mortality. PAPP-A levels were log-transformed for Normality. During 60-month follow-up, 37 (40%) of the 92 participants died. Higher PAPP-A was associated with increased risk of mortality in unadjusted analysis (HR per SD=1.4, 95% CI=1-1.9, P=.03) and when adjusted for confounders and cardiovascular risk factors (HR=1.8, 95% CI=1.18-2.73, P=.006). An interaction between PAPP-A levels and diabetes mellitus on mortality was found (HR for the multiplicative interaction term=2.74 95% CI=1.02-7.37, P=.05). In a quantile regression adjusted for age and sex, one SD increase in PAPP-A was associated with 22months shorter estimated time until 25% of the patients died (95% CI -35 to -9.1months). Increased PAPP-A levels are associated with higher all-cause mortality in prevalent haemodialysis patients with concomitant diabetes mellitus.