title: Pregnancy-associated plasma protein-A is a stronger predictor for adverse cardiovascular outcomes after acute coronary syndrome in type-2 diabetes mellitus.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Key Laboratory, Metabolic Disorders Related Cardiovascular Disease, Beijing, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Li
authors.affiliation: The Mountain-Whisper-Light Statistics, Seattle, WA, USA.
authors.forename: Moni B
authors.initials: MB
authors.lastname: Neradilek
authors.affiliation: Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Gu
authors.affiliation: Clinical Atherosclerosis Research Lab, Division of Cardiology, University of Washington, Seattle, WA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Isquith
authors.affiliation: Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Sun
authors.affiliation: Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wu
authors.affiliation: Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China. lhw19656@sina.com.|Key Laboratory, Metabolic Disorders Related Cardiovascular Disease, Beijing, China. lhw19656@sina.com.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Li
authors.affiliation: Clinical Atherosclerosis Research Lab, Division of Cardiology, University of Washington, Seattle, WA, USA. xueqiao@uw.edu.
authors.forename: Xue-Qiao
authors.initials: XQ
authors.lastname: Zhao
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000401:mortality; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000072658:Non-ST Elevated Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D010343:Patient Admission; D011237:Predictive Value of Tests; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D000072657:ST Elevation Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human
keywords: Acute coronary syndrome; Cardiovascular outcomes; Pregnancy-associated plasma protein-A; Type-2 diabetes mellitus