title: Pro-substance p for evaluation of risk in acute myocardial infarction.
abstract: BACKGROUND
  Pro-substance P (ProSP) is a stable surrogate marker for labile substance P, which has pro-inflammatory effects, increases platelet aggregation and clot strength, and reduces fibrinolysis.
  
  
  OBJECTIVE
  This study assessed whether ProSP was associated with poor prognosis after acute myocardial infarction (AMI) to identify novel pathophysiological mechanisms.
  
  
  METHODS
  ProSP was measured in 1,148 AMI patients (825 men, mean age 66.2 ± 12.8 years). Endpoints were major adverse cardiac events (composite of death, reinfarction, and heart failure [HF] hospitalization), death/reinfarction, and death/HF. GRACE (Global Registry of Acute Coronary Events) scores were compared with ProSP for death and/or reinfarction at 6 months.
  
  
  RESULTS
  During 2-year follow-up, there were 140 deaths, 112 HF hospitalizations, and 149 re-AMI. ProSP levels were highest on the first 2 days after admission and related to estimated glomerular filtration rate, age, history of diabetes, ischemic heart disease or hypertension, Killip class, left ventricular wall motion index, and sex. Multivariate Cox regression models showed ProSP level was a predictor of major adverse events (hazard ratio [HR]: 1.30; 95% confidence interval [CI]: 1.10 to 1.54; p < 0.002), death and/or AMI (HR: 1.42; 95% CI: 1.20 to 1.68; p < 0.0005), death and/or HF (HR: 1.38; 95% CI: 1.14 to 1.67; p < 0.001). ProSP levels with GRACE scores were independent predictors of 6-month death and/or reinfarction (p < 0.0005 for both). ProSP-adjusted GRACE scores reclassified patients significantly (overall category-free net reclassification improvement of 31.6 (95% CI: 14.3 to 49.0; p < 0.0005) mainly by down-classifying those without endpoints.
  
  
  CONCLUSIONS
  ProSP levels post-AMI are prognostic for death, recurrent AMI, or HF, and they improve risk prediction of GRACE scores, predominantly by down-classifying risk in those without events.
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom; National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom. Electronic address: lln1@le.ac.uk.
authors.forename: Leong L
authors.initials: LL
authors.lastname: Ng
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Jatinderpal K
authors.initials: JK
authors.lastname: Sandhu
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Hafid
authors.initials: H
authors.lastname: Narayan
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Paulene A
authors.initials: PA
authors.lastname: Quinn
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom; National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Iain B
authors.initials: IB
authors.lastname: Squire
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom; National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Joan E
authors.initials: JE
authors.lastname: Davies
authors.affiliation: Sphingotec, GmbH, Hennigsdorf, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.affiliation: Sphingotec, GmbH, Hennigsdorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergmann
authors.affiliation: Coronary Care Unit and Heart Failure Program, San Diego Veterans Affairs Medical Center, San Diego, California.
authors.forename: Alan
authors.initials: A
authors.lastname: Maisel
authors.affiliation: Department of Cancer Studies and Molecular Medicine, Leicester Royal Infirmary, University of Leicester, Leicester, United Kingdom.
authors.forename: Donald J L
authors.initials: DJ
authors.lastname: Jones
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis*; D012307:Risk Factors; D016037:Single-Blind Method; D013373:Substance P / Q000097:blood*
chemical_list: D015415:Biomarkers; D013373:Substance P
keywords: B-type natriuretic peptide; GRACE score; acute coronary syndrome(s); myocardial infarction; neurokinins; substance P