Redox‐generated isoprostanes are associated with residual platelet activity in aspirin‐treated patients with stable coronary heart disease

Redox‐generated isoprostanes are associated with residual platelet activity in aspirin‐treated patients with stable coronary heart disease

Aim: Insufficient platelet inhibition by low‐dose aspirin is associated with poor prognosis in patients with coronary heart disease (CHD). We sought to investigate the prevalence of this phenomenon in patients with stable CHD and to study whether oxidative stress plays a role in its pathogenesis. Me...

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Bibliographic Details
Published in:Journal of thrombosis and haemostasis Vol. 8; no. 12; pp. 2662 - 2670
Main Authors: SCHWEDHELM, E., BIEREND, A., MAAS, R., TRINKS, R., KOM, G. D., TSIKAS, D., BÖGER, R. H.
Format: Journal Article
Language:English
Published: Oxford, UK Blackwell Publishing Ltd 01-12-2010
Subjects:
Aged
aspirin
Aspirin - administration & dosage
Aspirin - therapeutic use
Blood Platelets - pathology
Coronary Disease - drug therapy
Coronary Disease - metabolism
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Female
Gas Chromatography-Mass Spectrometry
Humans
isoprostanes
Isoprostanes - biosynthesis
Isoprostanes - blood
Isoprostanes - urine
Male
Middle Aged
Oxidation-Reduction
Oxidative Stress
platelet aggregation
Platelet Aggregation Inhibitors - administration & dosage
Platelet Aggregation Inhibitors - therapeutic use
prognosis
Tandem Mass Spectrometry
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Summary:Aim: Insufficient platelet inhibition by low‐dose aspirin is associated with poor prognosis in patients with coronary heart disease (CHD). We sought to investigate the prevalence of this phenomenon in patients with stable CHD and to study whether oxidative stress plays a role in its pathogenesis. Methods and results: We studied the platelet response to long‐term (≥ 6 months) low‐dose (100 mg per day) aspirin in 130 consecutive patients with stable CHD (age 66 ± 8 years, 83% male). Among a wide distribution of platelet responses to collagen, ADP, and arachidonic acid, the vast majority of patients in the highest tertile of residual platelet activity (defined as ‘aspirin low‐responders’) were characterized by lack of platelet inhibition by aspirin in vitro, significantly although not completely suppressed platelet TXB2 production and COX‐1 activity, and significantly higher urinary 8‐iso‐prostaglandin F2α excretion [186 (147–230) vs. 230 (188–318) pg per mg creatinine; median (IQR), P < 0.001; measured by GC‐MS]. Conclusion: A relevant proportion of patients with CHD show insufficient platelet inhibition by low‐dose aspirin. Oxidative stress and lipid peroxidation causing isoprostane formation may underlie inadequate platelet inhibition in an aspirin‐insensitive manner in patients with cardiovascular disease.
Bibliography:These authors contributed equally to the manuscript.
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/j.1538-7836.2010.04117.x