European Heart Journal Advance Access originally published online on April 3, 2009
European Heart Journal 2009 30(10):1279-1286; doi:10.1093/eurheartj/ehp097
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COX-1 sensitivity and thromboxane A2 production in type 1 and type 2 diabetic patients under chronic aspirin treatment
1 Department of Experimental Medicine, ‘Sapienza’ University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
2 Institute of Cardiology, Catholic University, Rome, Italy
3 Department of Internal Medicine, Catholic University, Rome, Italy
Received 11 September 2008; revised 18 February 2009; accepted 26 February 2009; online publish-ahead-of-print 3 April 2009.
* Corresponding author. Tel: +39 (0) 6 49973002, Fax: +39 (0) 6 4454820, Email: fabio.pulcinelli{at}uniroma1.it
Aims: Although aspirin treatment is useful in reducing ischaemic events in diabetic patients, recent studies suggest that it is less effective when compared with non-diabetics (ND). We sought to evaluate COX-1 sensitivity and thromboxane A2 (TxA2) production in type 1 (T1DM) and type 2 diabetic (T2DM) patients under chronic aspirin treatment, and also evaluate the association between thromboxane A2 (TxA2) production and markers of inflammation and metabolic control, such as high-sensitivity C-reactive protein, fasting blood glucose, and haemoglobin A1c (HbA1c).
Methods and results: Agonist-induced platelet aggregation (PA) and TxB2, a stable metabolite of TxA2, production, serum TxB2, and platelet COX-1 and COX-2 expression were studied in T2DM patients, T1DM patients, and high-risk ND subjects, all receiving a low dose of aspirin. TxB2 formation was studied in platelets treated in vitro with aspirin alone or with a COX-2 inhibitor (NS-398). PA, collagen-induced TxB2 production, and serum TxB2 were higher in T1DM and T2DM patients than in ND subjects. TxB2 production was reduced in diabetic patients by in vitro treatment with aspirin. COX-2 was expressed in all diabetic patients but only in 46% of ND patients. In diabetic patients significant correlations were observed between TxB2 production and both fasting plasma glucose and HbA1c.
Conclusion: COX-1 sensitivity and TxB2 production is similarly reduced in both T1DM and T2DM patients under chronic aspirin treatment. The association between TxB2 production and either fasting plasma glucose and HbA1c levels suggests that in diabetic patients hyperglycaemia is a determinant of the reduced platelet sensitivity to aspirin.
Key Words: Diabetes • Aspirin • Cyclooxygenase • Platelets • Thromboxane
The first two authors contributed equally to the study.