Cell-Derived Microparticles in the Pathogenesis of Cardiovascular Disease Friend or Foe?

Microparticles are ascribed important roles in coagulation, inflammation, and endothelial function. These processes are mandatory to safeguard the integrity of the organism, and their derangements contribute to the development of atherosclerosis and cardiovascular disease. More recently, the presumed solely harmful role of microparticles has been challenged because microparticles may also be involved in the maintenance and preservation of cellular homeostasis and in promoting defense mechanisms. Here, we summarize recent studies revealing these 2 faces of microparticles in cardiovascular disease. (Arterioscler Thromb Vasc Biol. 2011;31:4-9.

Pharmacokinetic and Pharmacodynamic Variability of Fluindione in Octogenarians

In the PREPA observational study, we investigated the factors influencing pharmacokinetic and pharmacodynamic variability in the responses to fluindione, an oral anticoagulant drug, in a general population of octogenarian inpatients. Measurements of fluindione concentrations and international normalized ratio (INR) were obtained for 131 inpatients in whom fluindione treatment was initiated. Treatment was adjusted according to routine clinical practice. The data were analyzed using nonlinear mixed-effects modeling, and the parameters were estimated using MONOLIX 3.2. The pharmacokinetics (PK) of fluindione was monocompartmental, whereas the evolution of INR was modeled in accordance with a turnover model (inhibition of vitamin K recycling). Interindividual variability (IIV) was very large. Clearance decreased with age and with prior administration of cordarone. Patients who had undergone surgery before the study had lower IC50 values, leading to an increased sensitivity to fluindione. Pharmacokinetic exposure is substantially increased in elderly patients, warranting a lower dose of fluindione

Initial patency of the infarct-related artery in patients with acute ST elevation myocardial infarction is related to platelet response to aspirin

INTRODUCTION: A proportion of patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary angiography (PCI) presents with patent infarct-related artery (IRA) on initial angiography. We tested the hypothesis that stronger platelet response to aspirin in these patients at admission might be associated with higher initial coronary flow in the IRA. ----- METHODS: Platelet response to aspirin was assessed with Multiplate((R)) ASPI-test before coronary angiography in 70 patients on previous aspirin treatment admitted for acute STEMI. Coronary flow on initial angiogram was evaluated quantitatively according to the Thrombolysis in Myocardial Infarction (TIMI) grading system. Depending on the degree of arachidonic acid (AA) induced platelet aggregation in ASPI-test, patients were stratified into four quartiles and compared according to initial TIMI flow. ----- RESULTS: When TIMI flow was compared according to quartiles of platelet aggregation in ASPI-test, we have found significantly higher frequency of TIMI-2 and TIMI-3 flow among patients with low values of ASPI-test, i.e. with stronger aspirin response (P=0.014). None of the patients in the highest quartile of ASPI-test had TIMI flow of 2 or 3. ----- CONCLUSIONS: Patients with stronger antiplatelet response to aspirin therapy in acute STEMI are more likely to present with spontaneous IRA recanalization