Stable Coronary Artery Disease Controls Research Articles

Ticagrelor pharmacokinetics and pharmacodynamics in patients with NSTEMI after a 180-mg loading dose

The pharmacokinetics after a 180-mg loading dose (LD) of ticagrelor has not been thoroughly investigated in NSTEMI patients. We aimed to compare the ticagrelor uptake and on-treatment platelet reactivity between non-ST-segment elevation myocardial infarction (NSTEMI) patients and a control group of patients with stable coronary artery disease (SCAD) undergoing elective percutaneous coronary intervention. We performed an observational, prospective, single-center study including 40 NSTEMI patients and 20 SCAD controls. Key exclusion criteria included ongoing opioid treatment. Both groups received a 180-mg ticagrelor LD, and blood samples were taken pre-dose and 1, 2, 3, 4, 5, and 6 hours post-LD. Plasma concentrations of ticagrelor and its active metabolite AR-C124910XX were determined by validated methods. Platelet aggregation was tested using ADP-induced multiple electrode aggregometry. The primary endpoint was the time to maximal ticagrelor concentration (Tmax). Clinical trial registration identifier number: NCT02292277. None of the pharmacokinetic variables differed significantly between the groups, including the Tmax of ticagrelor (2.0h [1.0–3.0] versus 2.0h [2.0–3.0], p = 0.393) and the active metabolite AR-C124910XX (3.0 [2.0–4.0] versus 3.0 [2.5–4.0], p = 0.289). High on-treatment platelet reactivity (HPR) was defined as > 46 aggregation units and was at one hour seen in 15% of the NSTEMI patients versus 10% of the controls (p = 1.0). At two hours post the 180-mg ticagrelor LD, 3% of the NSTEMI patients had HPR compared with none of the controls (p = 1.0). In conclusion, the uptake of ticagrelor was not significantly slower in NSTEMI patients not receiving opioids compared with the SCAD controls, leading to adequate onset of platelet inhibition in both groups.

Novel potential biomarkers for ST-elevation myocardial infarction identified by proteomic analysis of plasma-derived microparticles

Purpose: Microparticles (MP) are cell-derived membrane vesicles of less than a micron known to be increased in the blood of patients with acute coronary syndromes. They derive from various cells, most notably platelets. Our objective was to compare the proteome of plasma-derived microparticles from ST-elevation myocardial infarction (STEMI) patients and stable coronary artery disease (SCAD) controls, and to detect MP proteins differentially regulated between both groups. Methods: Plasma MP were isolated from 10 STEMI patients and 10 SCAD matched controls. We followed a standardized procedure to guarantee the purity of the microparticle population. MPs were characterized by FACS and by electron microscopy. Proteome analysis was based on high-resolution two-dimensional differential in-gel electrophoresis (2D-DIGE) and mass spectrometry. Validations were by 1D- and 2D-western blotting in an independent cohort of patients. Results: For the proteomic analysis, samples were pooled for each condition (STEMI and SCAD), and four gels (technical replicates) were run. 1228 spots were detected per gel. The number of differentially regulated spots was of 223 (fold change ≥ 1.5 and p < 0.05). We focused on the analysis of 115 differentially regulated spots with a fold change ≥ 2 and p < 0.05. From those, 71 were up-regulated in MP from STEMI patients, whereas 44 were up-regulated in SCAD controls. Some of the differentially regulated proteins identified play a central role in the activation of the classical pathway of the complement system and are involved in inflammatory response (e.g. complement C3 and C4a). Others are important in the maintenance of hemostasis and participate in platelet activation (e.g. von Willebrand factor, fibrinogen, fibronectin). Another protein identified was alpha-2-macroglobulin, which plays an important role in thrombogenesis and has been recently found to be up-regulated in plasma MP from deep venous thrombosis patients. Interestingly, cardiotrophin-like cytokine factor 1 (CLCF1) was found to be up-regulated in STEMI samples. This is a cytokine with B-cell stimulating capability that we recently found to be present in platelet-derived MP. Conclusions: We performed the first high-resolution proteome analysis of plasma-derived MP from STEMI and SCAD patients. We provide a panel of proteins that vary between both conditions and that might constitute a promising source of biomarkers for STEMI.