Authors: Anfossi, Giovanni; Russo, Isabella; Trovati, Mariella

Source: Current Vascular Pharmacology, Volume 6, Number 4, October 2008 , pp. 313-328(16)

Publisher: Bentham Science Publishers

Abstract:

Platelets from patients affected by diabetes mellitus and metabolic syndrome show an impaired sensitivity to physiological antiaggregating agents and an enhanced activation state, mirrored by an increased expression of membrane activation markers; furthermore, they are more prone to form spontaneous microaggregates with ADP receptor involvement. These abnormalities are responsible for a pro-thrombotic condition, contributing to a high cardiovascular risk.

This pattern of platelet abnormalities provides a strong rationale for aggressive antiplatelet therapy strongly recommended by guidelines both in diabetes mellitus and in metabolic syndrome, not only in the setting of acute coronary syndromes, but also for the long-term prevention of the cardiovascular events.

Antiplatelet therapy in these pathological conditions, however, is still a matter of intense debate, especially because a high prevalence of “resistance” to these drugs (and to aspirin in particular) has been described in these patients. This may result in non-significant reductions in cardiovascular events.

Different factors seem to be involved, including: i) genetic polymorphisms; ii) hyperglycemia and poor metabolic control; iii) reduced sensitivity to nitric oxide; iv) a pro-inflammatory and/or pro-thrombotic status, and, v) increased oxidative stress.

This review will take into consideration: i) the results of the most relevant studies addressing the effects of the antiaggregating treatment in patients affected by diabetes mellitus and/or metabolic syndrome, and, ii) the biochemical mechanisms accounting for the impaired sensitivity to aspirin and thienopyridines in the above mentioned clinical conditions.

Keywords: Aspirin; cardiovascular disease; clopidogrel; metabolic syndrome; nitric oxide; obesity; platelets; thienopyridines; ticlopidine; type 2 diabetes mellitus

Document Type: Research article

DOI: http://dx.doi.org/10.2174/157016108785909760

Publication date: 2008-10-01

More about this publication?

• Vascular disease is the commonest cause of death in Westernized countries and its incidence is on the increase in developing countries. It follows that considerable research is directed at establishing effective treatment for acute vascular events. Long-term treatment has also received considerable attention (e.g. for symptomatic relief). Furthermore, effective prevention, whether primary or secondary, is backed by the findings of several landmark trials.
  
  Vascular disease is a complex field with primary care physicians and nurse practitioners as well as several specialties involved. The latter include cardiology, vascular and cardio thoracic surgery, general medicine, radiology, clinical pharmacology and neurology (stroke units). Current Vascular Pharmacology will publish reviews to update all those concerned with the treatment of vascular disease. For example, reviews commenting on recently published trials or new drugs will be included. In addition to clinically relevant topics we will consider 'research-based' reviews dealing with future developments and potential drug targets. Therefore, another function of Current Vascular Pharmacology is to bridge the gap between clinical practice and ongoing research.
  
  Debates will also be encouraged in the correspondence section of this journal.

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