Pregnancy-associated plasma protein A and mortality in haemodialysis

Abstract

Background: 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.

Materials and methods: 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.

Results: 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 22 months shorter estimated time until 25% of the patients died (95% CI -35 to -9.1 months).

Conclusions: Increased PAPP-A levels are associated with higher all-cause mortality in prevalent haemodialysis patients with concomitant diabetes mellitus.

Keywords: cardiovascular disease; haemodialysis; pregnancy-associated plasma protein A.