title: Improvement of risk assessment in systemic light-chain amyloidosis using human placental growth factor.
abstract: BACKGROUND
  Vascular amyloid deposition is common in light-chain amyloidosis resulting in endothelial dysfunction. Human placental growth factor (PlGF), a member of the vascular endothelial growth factor family was found to be altered in diverse pathological conditions, e.g. endothelial dysfunction. This study evaluated the clinical role of PlGF in light-chain amyloidosis.
  
  
  METHODS
  PlGF (cobas-PlGF, Roche Diagnostics, Mannheim, Germany) was analyzed in 125 consecutive patients with AL and correlated with diverse clinical parameters including mortality.
  
  
  RESULTS
  Kidney (n = 76) and heart (n = 57) were predominantly affected by amyloid deposition. Median PlGF was 26.3 (21.1-42.1) ng/L, NT-proBNP 3649 (1124-8581) pg/mL, and hs-TnT 42 (21-107) ng/L. PlGF increased with number of organs involved and with deterioration of renal function. A significant correlation of PlGF with hs-TnT (ρ = 0.306; p = 0.0007) and NT-proBNP (ρ = 0.315; p = 0.0006) was observed, but no correlation was observed with clinical, echocardiography, and electrocardiography parameters of cardiac involvement. In this cohort 1-year all-cause mortality was 19.2 %. The best cutoff discriminating survivors and non-survivors was 28.44 ng/L (sensitivity 66.7 %; specificity 78.1 %). A three-step risk model including hs-TnT and NT-proBNP revealed a better discrimination if patients at intermediary risk were additionally stratified by PlGF. Net reclassification index was 37.2 % (p = 0.002). Multivariate analysis revealed PlGF, difference of involved and uninvolved light chain, number of organs involved and risk class according to troponin T and NT-proBNP as independent predictors of mortality.
  
  
  CONCLUSIONS
  Plasma PlGF values in AL are invariably associated with the number of involved organs, but not with clinical, echocardiography, and electrocardiography parameters of cardiac involvement. PlGF provide useful information for risk stratification of patients at intermediary risk according to hs-TnT and NT-proBNP.
authors.affiliation: Department of Cardiology, Angiology, and Respiratory Medicine, Heidelberg University, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany, Arnt.Kristen@med.uni-heidelberg.de.
authors.forename: Arnt V
authors.initials: AV
authors.lastname: Kristen
authors.forename: Johannes
authors.initials: J
authors.lastname: Rinn
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: David
authors.initials: D
authors.lastname: Lindenmaier
authors.forename: Corina
authors.initials: C
authors.lastname: Merkle
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.forename: Stefan
authors.initials: S
authors.lastname: Hardt
authors.forename: Evangelos
authors.initials: E
authors.lastname: Giannitsis
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
mesh_terms: D000368:Aged; D000686:Amyloidosis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D018450:Disease Progression; D005260:Female; D005858:Germany; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000072483:Placenta Growth Factor; D011237:Predictive Value of Tests; D011257:Pregnancy Proteins / Q000097:blood*; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D007147:Immunoglobulin Light Chains; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor