title: Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome.
abstract: BACKGROUND
  Evaluation of patients who present to the hospital with a complaint of chest pain or other signs or symptoms suggestive of acute coronary syndrome (ACS) is time-consuming, expensive, and problematic. Recent investigations have indicated that increases in biomarkers upstream from biomarkers of necrosis (cardiac troponins I and T), such as inflammatory cytokines, cellular adhesion molecules, acute-phase reactants, plaque destabilization and rupture biomarkers, biomarkers of ischemia, and biomarkers of myocardial stretch may provide earlier assessment of overall patient risk and aid in identifying patients with higher risk of an adverse event.
  The purpose of this review is to provide an overview of the pathophysiology and clinical and analytical characteristics of several biomarkers that may have potential clinical utility to identify ACS patients. These biomarkers (myeloperoxidase, metalloproteinase-9, soluble CD40 ligand, pregnancy-associated plasma protein A, choline, ischemia-modified albumin, unbound free fatty acids, glycogen phosphorylase isoenzyme BB, and placental growth factor) have demonstrated promise and need to be more thoroughly evaluated for commercial development for implementation into routine clinical and laboratory practice.
  
  
  CONCLUSIONS
  Specifications that have been addressed for cardiac troponins and natriuretic peptides will need to be addressed with the same scrutiny for the biomarkers discussed in this review. They include validating analytical imprecision and detection limits, calibrator characterization, assay specificity and standardization, pre-analytical issues, and appropriate reference interval studies. Crossing boundaries from research to clinical application will require replication in multiple settings and experimental evidence supporting a pathophysiologic role and, ideally, interventional trials demonstrating that monitoring single or multiple biomarkers improves outcomes.
authors.affiliation: Department of Laboratory Medicine and Pathology, Clinical Laboratories, Hennepin County Medical Center, Minneapolis, MN 55415, USA. fred.apple@co.hennepin.mn.us
authors.forename: Fred S
authors.initials: FS
authors.lastname: Apple
authors.forename: Alan H B
authors.initials: AH
authors.lastname: Wu
authors.forename: Johannes
authors.initials: J
authors.lastname: Mair
authors.forename: Jan
authors.initials: J
authors.lastname: Ravkilde
authors.forename: Mauro
authors.initials: M
authors.lastname: Panteghini
authors.forename: Jillian
authors.initials: J
authors.lastname: Tate
authors.forename: Franca
authors.initials: F
authors.lastname: Pagani
authors.forename: Robert H
authors.initials: RH
authors.lastname: Christenson
authors.forename: Martin
authors.initials: M
authors.lastname: Mockel
authors.forename: Oliver
authors.initials: O
authors.lastname: Danne
authors.forename: Allan S
authors.initials: AS
authors.lastname: Jaffe
mesh_terms: D000208:Acute Disease; D000418:Albumins / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000097:blood; D002637:Chest Pain / Q000175:diagnosis; D002794:Choline / Q000097:blood; D003327:Coronary Disease / Q000175:diagnosis* / Q000517:prevention & control; D003937:Diagnosis, Differential; D005230:Fatty Acids, Nonesterified / Q000097:blood; D025002:Glycogen Phosphorylase, Brain Form / Q000097:blood; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D009195:Peroxidase / Q000097:blood; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis; D012016:Reference Values; D018570:Risk Assessment
chemical_list: D000418:Albumins; D015415:Biomarkers; D005230:Fatty Acids, Nonesterified; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D023201:CD40 Ligand; D009195:Peroxidase; D025002:Glycogen Phosphorylase, Brain Form; D011266:Pregnancy-Associated Plasma Protein-A; D020780:Matrix Metalloproteinase 9; D002794:Choline