Pregnancy-associated plasma protein-A is a stronger predictor for adverse cardiovascular outcomes after acute coronary syndrome in type-2 diabetes mellitus

Cardiovasc Diabetol. 2017 Apr 5;16(1):45. doi: 10.1186/s12933-017-0526-6.

Abstract

Background: The risk prediction of pregnancy-associated plasma protein-A (PAPP-A) for future cardiovascular (CV) events post acute coronary syndrome (ACS) in patients with type-2 diabetes mellitus (T2DM) was investigated in comparison to other risk factors.

Methods: PAPP-A was measured at hospital admission in 320 consecutive ACS patients (136 with T2DM and 184 without). All patients were followed for 2 years for occurrence of CV death, non-fatal MI or stroke. Effect of PAPP-A on the CV event risk was estimated using Cox regression models. Receiver operating characteristics (ROC) curves were generated to demonstrate the sensitivity and specificity of PAPP-A in predicting CV events.

Results: ACS patients with T2DM had higher PAPP-A (19.29 ± 16.36 vs. 13.29 ± 13.90 ng/ml, p < 0.001) and higher rate of CV events 2 years post ACS (27.2 vs. 13.6%, p = 0.002) than those without. Higher levels of PAPP-A were significantly associated with increased risk of CV events during 2-year follow-up [HR = 2.97 for 1 SD increase in log10(PAPP-A), 95% CI 2.11-4.18, p < 0.001] in T2DM and (HR = 3.16, 95% CI 2.27-4.39, p < 0.001) in non-T2DM. Among patients with T2DM, PAPP-A showed a larger area under the curve (AUC 0.79) that was significantly more predictive than hsCRP (AUC 0.64), eGFR (AUC 0.66) and LVEF < 50% (AUC 0.52); predictive ability did not improve significantly by including those factors into the model.

Conclusions: Patients with T2DM had higher levels of PAPP-A and increased risk of CV events. Elevated PAPP-A compared to other risk factors was a stronger predictor for future CV events 2 years post ACS in patients with T2DM. Trial registration ISRCTN10805074. Registered on 20 January 2017, retrospectively registered.

Keywords: Acute coronary syndrome; Cardiovascular outcomes; Pregnancy-associated plasma protein-A; Type-2 diabetes mellitus.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / etiology
  • Acute Coronary Syndrome / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Biomarkers / blood
  • Case-Control Studies
  • Chi-Square Distribution
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / mortality
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Non-ST Elevated Myocardial Infarction / blood
  • Non-ST Elevated Myocardial Infarction / diagnosis
  • Non-ST Elevated Myocardial Infarction / etiology*
  • Non-ST Elevated Myocardial Infarction / mortality
  • Patient Admission
  • Predictive Value of Tests
  • Pregnancy-Associated Plasma Protein-A / analysis*
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • ROC Curve
  • Recurrence
  • Risk Assessment
  • Risk Factors
  • ST Elevation Myocardial Infarction / blood
  • ST Elevation Myocardial Infarction / diagnosis
  • ST Elevation Myocardial Infarction / etiology*
  • ST Elevation Myocardial Infarction / mortality
  • Time Factors
  • Up-Regulation

Substances

  • Biomarkers
  • Pregnancy-Associated Plasma Protein-A
  • PAPPA1 protein, human

Associated data

  • ISRCTN/ISRCTN10805074