title: Thromboxane and prostacyclin biosynthesis in heart failure of ischemic origin: effects of disease severity and aspirin treatment.
abstract: BACKGROUND
  Thromboembolism is a relatively common complication of chronic heart failure (HF) and the place of antiplatelet therapy is uncertain.
  
  
  OBJECTIVE
  We characterized the rate of thromboxane and prostacyclin biosynthesis in chronic HF of ischemic origin, with the aim of separating the influence of HF on platelet activation from that of the underlying ischemic heart disease (IHD).
  
  
  METHODS
  We compared urinary 11-dehydro-thromboxane (TX)B(2), 2,3 dinor 6-keto-PGF(1alpha,) 8-iso-prostaglandin (PG)F(2alpha), and plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP), asymmetric dimethylarginine (ADMA), and soluble CD40 ligand (sCD40L), in 84 patients with HF secondary to IHD, 61 patients with IHD without HF and 42 healthy subjects.
  
  
  RESULTS
  HF patients not on aspirin had significantly higher urinary 11-dehydro-TXB(2) as compared with healthy subjects (P < 0.0001) and IHD patients not on aspirin (P = 0.028). They also showed significantly higher 8-iso-PGF(2alpha) (P = 0.018), NT-pro-BNP (P = 0.021) and ADMA (P < 0.0001) than IHD patients not on aspirin. HF patients on low-dose aspirin had significantly lower 11-dehydro-TXB(2) (P < 0.0001), sCD40L (P = 0.007) and 2,3-dinor-6-keto-PGF(1alpha) (P = 0.005) than HF patients not treated with aspirin. HF patients in NYHA classes III and IV had significantly higher urinary 11-dehydro-TXB(2) than patients in classes I and II, independently of aspirin treatment (P < 0.05). On multiple linear regression analysis, higher NT-pro-BNP levels, lack of aspirin therapy and sCD40L, predicted 11-dehydro-TXB(2) excretion rate in HF patients (R(2) = 0.771).
  
  
  CONCLUSIONS
  Persistent platelet activation characterizes HF patients. This phenomenon is related to disease severity and is largely suppressable by low-dose aspirin. The homeostatic increase in prostacyclin biosynthesis is impaired, possibly contributing to enhanced thrombotic risk in this setting.
authors.affiliation: Center of Excellence on Aging, G D'Annunzio University Foundation, Chieti, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Santilli
authors.forename: G
authors.initials: G
authors.lastname: Davì
authors.forename: S
authors.initials: S
authors.lastname: Basili
authors.forename: S
authors.initials: S
authors.lastname: Lattanzio
authors.forename: A
authors.initials: A
authors.lastname: Cavoni
authors.forename: G
authors.initials: G
authors.lastname: Guizzardi
authors.forename: L
authors.initials: L
authors.lastname: De Feudis
authors.forename: G
authors.initials: G
authors.lastname: Traisci
authors.forename: C
authors.initials: C
authors.lastname: Pettinella
authors.forename: L
authors.initials: L
authors.lastname: Paloscia
authors.forename: P
authors.initials: P
authors.lastname: Minuz
authors.forename: A
authors.initials: A
authors.lastname: Meneguzzi
authors.forename: G
authors.initials: G
authors.lastname: Ciabattoni
authors.forename: C
authors.initials: C
authors.lastname: Patrono
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism*; D012720:Severity of Illness Index; D013931:Thromboxanes / Q000096:biosynthesis*
chemical_list: D013931:Thromboxanes; D011464:Epoprostenol; D001241:Aspirin