Abstract
Background: Aspirin is the most commonly used antiplatelet agent for the prevention of cardiovascular diseases. However, a certain proportion of patients do not respond to aspirin therapy. The mechanisms of aspirin non-response remain unknown. The unique metabolomes in platelets of patients with coronary artery disease (CAD) with aspirin non-response may be one of the causes of aspirin resistance.Materials and Methods: We enrolled 29 patients with CAD who were aspirin non-responders, defined as a study subject who were taking aspirin with a platelet aggregation time less than 193 s by PFA-100, and 31 age- and sex-matched patients with CAD who were responders. All subjects had been taking 100 mg of aspirin per day for more than 1 month. Hydrophilic metabolites from the platelet samples were extracted and analyzed by nuclear magnetic resonance (NMR). Both 1D 1H and 2D J-resolved NMR spectra were obtained followed by spectral processing and multivariate statistical analysis, such as partial least squares discriminant analysis (PLS-DA).Results: Eleven metabolites were identified. The PLS-DA model could not distinguish aspirin non-responders from responders. Those with low serum glycine level had significantly shorter platelet aggregation time (mean, 175.0 s) compared with those with high serum glycine level (259.5 s). However, this association became non-significant after correction for multiple tests.Conclusions: The hydrophilic metabolic profile of platelets was not different between aspirin non-responders and responders. An association between lower glycine levels and higher platelet activity in patients younger than 65 years suggests an important role of glycine in the pathophysiology of aspirin non-response.
Highlights
Cardiovascular diseases are the most common cause of mortality and morbidity worldwide
Accumulation of platelets at the site of atherosclerotic lesion disruption is the first step in the formation of atherothrombosis; these elements are responsible for the formation of pathogenic thrombi in patients with atherothrombotic diseases, such as coronary artery disease (CAD), ischemic stroke/transient ischemic attack (TIA), and peripheral artery disease (PAD)
There is no significant difference in mean age, distribution of sex, body mass index, serum level of hemoglobin, platelet, total cholesterol, triglyceride, and percentage of patients with hypertension and diabetes mellitus (DM) between aspirin responders and non-responders (Table 1)
Summary
Cardiovascular diseases are the most common cause of mortality and morbidity worldwide. Atherothrombosis, characterized by atherosclerotic lesion disruption with thrombotic complications, is the main cause of acute cardiovascular events. Aspirin is by far the most commonly used antiplatelet agent for the prevention of cardiovascular diseases. Stejskal et al reported that patients with acute coronary syndrome and aspirin nonresponse had an 88% incidence of recurrent cardiovascular events compared with 47% in aspirin responders (Stejskal et al, 2006). Gum et al showed that aspirin non-response was significantly associated with an increased risk of major cardiovascular adverse event (24% vs 10%, hazard ratio 3.12) (Gum et al, 2003). Aspirin is the most commonly used antiplatelet agent for the prevention of cardiovascular diseases. The unique metabolomes in platelets of patients with coronary artery disease (CAD) with aspirin nonresponse may be one of the causes of aspirin resistance
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