Platelet reactivity and response to aspirin in subjects with the metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) is associated with a prothrombotic state and predicts the subsequent development of type 2 diabetes mellitus. We hypothesized that similar to diabetes, subjects with MS may have increased platelet reactivity, and reduced response to aspirin. We, therefore, compared platelet reactivity and response to aspirin among subjects with MS and healthy volunteers. METHODS: Fifty subjects with MS, defined by Adult Treatment Panel III criteria (age 44+/-9 years, 80% women, body mass index 35+/-8 kg/m2) were compared to 50 healthy controls who met none of the MS criteria (age 40+/-7 years, 80% women, body mass index: 24+/-3 kg/m2). Blood samples were taken before and 24 hours after 325 mg aspirin (single dose). Platelet function was evaluated by aggregation in response to 1.5 mmol/L arachidonic acid, 1 microg/mL collagen, and 5 and 20 micromol/L adenosine diphosphate; the VerifyNow Aspirin assay (Accumetrics Inc, San Diego, CA); Impact-R Cone and Plate(let) Analyzer (shear-dependent test) (DiaMed, Cresier, Switzerland) and flow cytometric determination of P-selectin expression and activated glycoprotein IIb/IIIa expression; and reticulated platelets (reflecting platelet turnover). RESULTS: Subjects with MS had higher baseline P-selectin levels (14.5+/-5 vs 11.3+/-4 mean fluorescence intensity, P=.002), reticulated platelets (2.8%+/-3% vs 1.2%+/-1%, P=.04) and platelet deposition under flow (Impact-R 7.5%+/-2% vs 5.9%+/-2%, P=.003). Subjects with MS also had lower response to aspirin, as evaluated by the change in all platelet aggregation assays and the VerifyNow score. CONCLUSIONS: Subjects with MS appear to have increased baseline platelet reactivity and turnover and a lower antiplatelet response to aspirin. Further research is required to elucidate platelet properties in subjects with MS and find ways to modify them.

Platelet reactivity in patients with subacute stent thrombosis compared with non-stent-related acute myocardial infarction.

BACKGROUND: Recent case control studies suggest that patients with subacute stent thrombosis (SAT) have increased platelet reactivity. However, SAT often presents as acute myocardial infarction (AMI), which is also associated with augmented platelet activation. We therefore compared platelet reactivity in patients with SAT and patients with AMI unrelated to stenting. METHODS: We identified 20 patients with SAT, 20 patients with ST-elevation AMI who underwent primary percutaneous coronary intervention (PCI), and 20 patients who underwent stenting without SAT occurrence (stable control group). Platelet function was measured > or = 3 days after PCI in the SAT (repeat procedure) and AMI groups and > or = 3 months after stenting in the stable group. All patients received aspirin and clopidogrel. Platelet reactivity was evaluated by aggregation in response to 5 and 20 micromol/L of adenosine diphosphate and 1.5 mmol/L arachidonic acid, and by flow cytometric determination of P-selectin and glycoprotein IIb/IIIa activation. RESULTS: Clinical characteristics were similar among the groups. Platelet testing was performed 4.9 +/- 1.7, 3.1 +/- 0.3, and 108 +/- 22 days after PCI in the SAT, AMI, and stable groups, respectively. The SAT group had higher platelet aggregation and activation markers than the stable group. However, platelet aggregation and activation was very similar in the SAT and AMI groups. CONCLUSIONS: Patients with SAT have increased platelet reactivity, compared with patients who do not develop SAT following stenting. However, the augmented platelet reactivity does not appear to differ from patients with AMI unrelated to stenting. This study highlights the need for large prospective studies to determine whether platelet hyperreactivity increases the risk of SAT.

Effect of caffeine on platelet inhibition by clopidogrel in healthy subjects and patients with coronary artery disease.

BACKGROUND: Clopidogrel inhibits the platelet P2Y12 receptor, leading to increased intracellular cyclic AMP (cAMP) levels. Caffeine also causes a rise in platelet cAMP. We aimed to test the effect of acute caffeine administration on platelet inhibition by clopidogrel, in healthy volunteers and patients with coronary artery disease. METHODS: Cohort 1: 12 healthy subjects were enrolled in a 2-week crossover study. Blood samples were drawn at baseline, 2, 4, and 24 hours after 300 mg clopidogrel intake. At the first week, 6 subjects received caffeine (300 mg pill, equivalent to a medium sized coffee drink) 30 minutes after clopidogrel. At week 2, the other 6 subjects received caffeine. One month later the effect of caffeine alone was tested. Platelet function was evaluated by aggregation in response to 5, 10, and 20 micromol/L adenosine diphosphate, 1 microg/mL collagen, and flow cytometric determination of P-selectin expression, PAC-1 binding, and vasodilator-stimulated phosphoprotein phosphorylation. Cohort 2: 40 patients with coronary artery disease receiving aspirin and clopidogrel (75 mg daily) for > or = 1 week were tested at baseline and 2.5 hours after caffeine (300 mg). RESULTS: In cohort 1 (crossover study), caffeine was associated with lower adenosine diphosphate-induced aggregation at 4 hours, lower activation markers at 2 hours, and lower vasodilator-stimulated phosphoprotein phosphorylation at 4 hours after clopidogrel. Caffeine alone had no effect on the assessed platelet surface biomarkers. In cohort 2, caffeine administration was associated with lower platelet activation markers (P-selectin, PAC-1 binding), without significant effect on aggregation. CONCLUSIONS: Acute caffeine administration after clopidogrel loading appears to be associated with enhanced platelet inhibition 2 to 4 hours after clopidogrel intake. The mechanism probably involves synergistic increase in cAMP levels.