Background: Thromboembolism is a relatively common complication of chronic heart failure (HF) and the place of antiplatelet therapy is uncertain. Objectives: We characterized the rate of thromboxane and prostacyclin biosynthesis in chronic HF of ischemic origin, with the aim of dissecting out the influence of HF on platelet activation from that of the underlying ischemic heart disease (IHD). Patients and 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 to 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), 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 class III-IV had significantly higher urinary 11-dehydro-TXB(2) than patients in I-II class, 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.

Thromboxane and prostacyclin biosynthesis in heart failure of ischemic origin: effects of disease severity and aspirin treatment.

MINUZ, Pietro;MENEGUZZI, Alessandra;
2010-01-01

Abstract

Background: Thromboembolism is a relatively common complication of chronic heart failure (HF) and the place of antiplatelet therapy is uncertain. Objectives: We characterized the rate of thromboxane and prostacyclin biosynthesis in chronic HF of ischemic origin, with the aim of dissecting out the influence of HF on platelet activation from that of the underlying ischemic heart disease (IHD). Patients and 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 to 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), 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 class III-IV had significantly higher urinary 11-dehydro-TXB(2) than patients in I-II class, 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.
2010
aspirin; heart failure; prostacyclin; thromboxane; ventricular stress
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/342975
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