Prognostic Values of Pregnancy-Associated Plasma Protein-A and IGF-Binding Protein-4 Fragments in Patients with Acute Myocardial Infarction

Background: Pregnancy-associated plasma protein-A (PAPP-A)-derived N- and C-terminal fragments of IGF-binding protein-4 (NT- and CT-IGFBP-4) are released from vulnerable atherosclerotic plaques. This study investigated the prognostic value of PAPP-A and IGFBP-4 fragments in patients with acute myocardial infarction (AMI), especially in those combined with chronic kidney disease (CKD). Methods: This prospective study measured admission levels of PAPP-A, NT- and CT-IGFBP-4 in 341 consecutive AMI patients. Of these patients, 232 were diagnosed with CKD (AMI and CKD), which consisted predominantly of early-stage cases. The primary outcome was one-year major adverse cardiovascular and cerebrovascular events (MACCE), a composite of cardiovascular death, non-fatal MI, and stroke. Results: In the whole AMI cohort and the AMI and CKD subgroup, serum PAPP-A and NT-IGFBP-4 levels in patients with MACCE were both significantly higher than those in patients without MACCE, whereas CT-IGFBP-4 levels were similar. Multivariable Cox regression analysis revealed that increased levels of PAPP-A (HR, 2.48; 95% CI, 1.09–5.63; p = 0.030) and NT-IGFBP-4 (HR, 2.48; 95% CI, 1.03–6.02; p = 0.044) were associated with MACCE in the whole AMI cohort. The areas under the receiver operating characteristic (ROC) curve for PAPP-A and NT-IGFBP-4 were 0.637 and 0.633, respectively. However, in the AMI and CKD subgroups, only NT-IGFBP-4 was identified as an independent predictor of MACCE (HR, 2.72; 95% CI, 1.16–6.41; p = 0.021) and cardiovascular death (HR, 2.63; 95% CI, 1.01–6.84; p = 0.048). Conclusions: PAPP-A and NT-IGFBP-4 were independently associated with one-year MACCE. NT-IGFBP-4 may be a promising prognostic marker in AMI patients with early-stage CKD.