Resistance to aspirin and thienopyridines in diabetes mellitus and metabolic syndrome.
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 anti-aggregating 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.
Diabetes Unit, Department of Clinical and Biological Sciences of the University of Turin, San Luigi Gonzaga Hospital, 10043 Orbassano Turin, Italy. giovanni.anfossi@unito.it
Giovanni
G
Anfossi
Isabella
I
Russo
Mariella
M
Trovati
D001241:Aspirin / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy*; D004351:Drug Resistance; D006801:Humans; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D012307:Risk Factors
D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C446540:thienopyridine; D001241:Aspirin