title: Osteopontin: a novel predictor of survival in patients with systemic light-chain amyloidosis.
abstract: BACKGROUND
  Troponin-T (cTnT) and NT-proBNP provide prognostic information in light-chain amyloidosis (AL). Thus, these biomarkers are widely used in clinical routine for risk stratification. Recently, plasma level of osteopontin (OPN), a secreted phosphoglycoprotein expressed by a variety of cell types, has been reported as a risk predictor in various cardiovascular diseases.
  
  
  METHODS
  OPN was determined retrospectively in 150 consecutive patients newly diagnosed with AL amyloidosis. All patients were evaluated according to a routine protocol including electrocardiography, echocardiography and laboratory testing.
  
  
  RESULTS
  Mean OPN was 591 ± 37 ng/mL. Cardiac involvement was established in 83 (55.3%). Median OPN plasma level were associated with number of organs involved, renal function, eligibility for high-dose melphalan chemotherapy and autologous stem cell transplantation, and severity of cardiac amyloidosis. Median follow-up was 19.2 months. 1-year all-cause-survival was 83.4%. The cut-offs discriminating 1-year all-cause-mortality for NT-proBNP, troponin T, and OPN were 2544 ng/L, 0.035 µg/L, and 426.8 ng/mL, respectively. Outcome was worse in patients with biomarkers above the individual ROC derived cut-off. A significant improvement of survival was observed in patients with cTNT >0.035 µg/L or NT-proBNP >2544 ng/L and OPN below ROC-derived cut-off of 426.8 ng/mL as compared to patients with OPN above 426.8 ng/L. No further discrimination was achieved by OPN in the cohorts of low troponin T or low NT-proBNP, respectively. Separate multivariate models identified OPN (cut-off 426.8 ng/mL) and troponin T (cut-off 0.035 µg/L) as independent predictors of all-cause-mortality.
  
  
  CONCLUSIONS
  These data demonstrated that OPN appears to be a valuable marker in the clinical routine for evaluation of patients with AL amyloidosis, especially if it is used in combination with cTNT and/or NT-proBNP.
authors.affiliation: Department of Cardiology, Angiology, and Respiratory Medicine, Heidelberg University , Heidelberg , Germany .
authors.forename: Arnt V
authors.initials: AV
authors.lastname: Kristen
authors.forename: Mark
authors.initials: M
authors.lastname: Rosenberg
authors.forename: David
authors.initials: D
authors.lastname: Lindenmaier
authors.forename: Corina
authors.initials: C
authors.lastname: Merkle
authors.forename: Henning
authors.initials: H
authors.lastname: Steen
authors.forename: Florian
authors.initials: F
authors.lastname: Andre
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Schönland
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Schnabel
authors.forename: Tibor
authors.initials: T
authors.lastname: Schuster
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.forename: Evangelos
authors.initials: E
authors.lastname: Giannitsis
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Norbert
authors.initials: N
authors.lastname: Frey
mesh_terms: D000368:Aged; D000686:Amyloidosis / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood / Q000235:genetics; D000075363:Immunoglobulin Light-chain Amyloidosis; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood* / Q000235:genetics; D053495:Osteopontin / Q000097:blood* / Q000235:genetics; D010446:Peptide Fragments / Q000097:blood* / Q000235:genetics; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D014182:Transplantation, Autologous; D020107:Troponin T / Q000097:blood* / Q000235:genetics
chemical_list: D018906:Antineoplastic Agents, Alkylating; D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D053495:Osteopontin; D020097:Natriuretic Peptide, Brain; D008558:Melphalan
keywords: Amyloid; biomarker; natriuretic peptide; osteopontin; survival; troponin T