Platelet dysfunction in central obesity.

Central obesity is a relevant risk factor for major cardiovascular events due to the atherosclerotic involvement of coronary, cerebral and lower limb arterial vessels. A major role in the increased cardiovascular risk is played by platelets, which show an increased activation and a reduced sensitivity to the physiological and pharmacological antiaggregating agents. This review focuses on platelet dysfunction in central obesity. The mechanisms involved are related to: i) the reduced sensitivity to insulin and other substances acting via intracellular cyclic nucleotides, such as nitrates and prostacyclin; ii) the altered intracellular ionic milieu with elevated cytosolic Ca(2+); and iii) the increased oxidative stress, which elicits isoprostane production from arachidonic acid. Therapeutic guidelines recommend a multifactorial prevention of cardiovascular disease including antiplatelet drugs in high risk patients, even though, at present, the protective effect of antiplatelet therapy in obese, insulin resistant subjects has not been evaluated by specific trials. Some reports, however, suggest a decreased sensitivity to the antiaggregating effects of both acetylsalicylic acid (aspirin) and thienopyridines in human obesity. Platelet defects may play a pivotal role in the reduced efficacy of antiplatelet therapy in obese subjects in the setting of cardiovascular prevention and acute coronary syndrome treatment. Thus, a specifically tailored antiaggregating therapy is likely necessary in obese, insulin resistant subjects, especially in the presence of type 2 diabetes mellitus.