Średnia objętość płytek krwi i wskaźnik dużych komórek jako czynniki prognostyczne choroby wieńcowej i zawału serca

Platelets represent an important link between inflammation and thrombosis and play an important role in all stages of atherosclerotic lesion formation. Increased platelet activity and their tendency to clot formation favour the incidence of thrombotic complications, such as unstable angina pectoris (UA), myocardial infarction (MI) and sudden cardiac death, in the course of coronary artery disease (CAD). Mean platelet volume (MPV) reflects the average size of platelets and, under normal circumstances, ranges between 7.5 fL to 10.5 fL. Platelet-large cell ratio (P-LCR) is defined as the percentage of platelets that exceed the normal value of platelet volume of 12 fL in the total platelet count. Platelet size has been shown to reflect platelet activity; therefore MPV and P-LCR are a simple and easy method of indirect assessment of platelet stimulation. In general population, higher MPV values are associated with increased risk of CAD. Higher MPV and P-LCR values are observed in CAD patients compared to patients without coronary atherosclerosis. In acute coronary syndromes (ACS) the MPV value is higher in patients with myocardial infarction than in patients with unstable CAD. In cases of stable CAD, elevated MPV correlates with the severity of coronary artery involvement and is a predictive factor of ACS. In patients with acute MI high MPV value has been reported to have impact on the no-reperfusion phenomenon following a percutaneous coronary intervention (PCI). Therefore, MPV and P-LCR indices, combined with other prognostic parameters, may be an important element of various scoring systems used in long-term prognosis in both stable CAD and ACS.Płytki krwi są ważnym ogniwem łączącym zapalenie i zakrzepicę oraz odgrywają istotną rolę na wszystkich etapach powstawania zmian miażdżycowych. Zwiększona aktywność płytek krwi powodująca nasiloną krzepliwość krwi przyczynia się do większej liczby powikłań zakrzepowych, takich jak niestabilna dławica piersiowa (UA), zawał serca (MI) i nagły zgon sercowy w przebiegi choroby wieńcowej (CAD). Średnia objętość płytki krwi (MPV) odpowiada przeciętnej wielkości płytek i w normalnych warunkach mieści się w zakresie od 7,5 fl do 10,5 fl. Wskaźnik płytkowy dużych komórek (P-LCR) jest definiowany jako odsetek płytek krwi przekraczających zakres prawidłowej objętości płytek wynoszący powyżej 12 fl. Wykazano, że wielkość płytek odzwierciedla ich aktywność, dlatego oznaczenie MPV i P-LCR to proste i łatwe metody pośredniej oceny stopnia stymulacji płytek krwi. W populacji ogólnej wyższe wartości MPV wiążą się ze zwiększonym ryzykiem CAD. U chorych z CAD obserwuje się wyższe wartości MPV i P-LCR niż u osób bez zmian miażdżycowych tętnic wieńcowych. W grupie chorych z ostrymi zespołami wieńcowymi (ACS) wartość MPV jest wyższa u osób z rozpoznaniem zawału serca niż u osób z niestabilną CAD. W przypadku stabilnej CAD wielkość MPV koreluje z ciężkością zmian w tętnicach wieńcowych i jest czynnikiem predykcyjnym ACS. Opisywano wpływ wysokich wartości MPV u chorych z ostrym MI na występowanie zjawiska braku reperfuzji po przezskórnej interwencji wieńcowej (PCI). Dlatego wskaźniki MPV i P-LCR w połączeniu z innymi prognostycznymi parametrami mogą być ważnym elementem różnych systemów oceny ryzyka w perspektywie długookresowej zarówno w stabilnej CAD, jak i ACS

The Role of Platelet-Derived Growth Factor Signaling in Healing Myocardial Infarcts

ObjectivesThis study sought to examine the role of platelet-derived growth factor (PDGF) signaling in healing myocardial infarcts.BackgroundPlatelet-derived growth factor isoforms exert potent fibrogenic effects through interactions with PDGF receptor (PDGFR)-α and PDGFR-β. In addition, PDGFR-β signaling mediates coating of developing vessels with mural cells, leading to the formation of a mature vasculature. We hypothesized that PDGFR activation may regulate fibrosis and vascular maturation in healing myocardial infarcts.MethodsMice undergoing reperfused infarction protocols were injected daily with a neutralizing anti–PDGFR-β antibody (APB5), an anti-PDGFR-α antibody (APA5), or control immunoglobulin G, and were killed after 7 days of reperfusion.ResultsThe PDGF-B, PDGFR-α, and PDGFR-β mRNA expression was induced in reperfused mouse infarcts. Perivascular cells expressing phosphorylated PDGFR-β were identified in the infarct after 7 days of reperfusion, indicating activation of the PDGF-BB/PDGFR-β pathway. The PDGFR-β blockade resulted in impaired maturation of the infarct vasculature, enhanced capillary density, and formation of dilated uncoated vessels. Defective vascular maturation in antibody-treated mice was associated with increased and prolonged extravasation of red blood cells and monocyte/macrophages, suggesting increased permeability. These defects resulted in decreased collagen content in the healing infarct. In contrast, PDGFR-α inhibition did not affect vascular maturation, but significantly decreased collagen deposition in the infarct.ConclusionsPlatelet-derived growth factor signaling critically regulates postinfarction repair. Both PDGFR-β– and PDGFR-α–mediated pathways promote collagen deposition in the infarct. Activation of PDGF-B/PDGFR-β is also involved in recruitment of mural cells by neovessels, regulating maturation of the infarct vasculature. Acquisition of a mural coat and maturation of the vasculature promotes resolution of inflammation and stabilization of the scar

Benefits of the selective invasive strategy guided by CTA and CT-FFR in patients with coronary artery disease

Background: Coronary computed tomography angiography (CTA) has high diagnostic accuracy in ruling out significant stenosis of coronary arteries. The additional use of CTA- derived FFR further enhances diagnostic utility of coronary CTA. Some of the patients interrogated non-invasively have diseased coronary arteries and undergo further diagnostic testing, including invasive coronary angiography (ICA). Patients with one vessel disease may benefit from invasive interrogation limited to the diseased vessel only. Aims: In 100 patients, we analysed the impact of a “diseased-vessel-only”, selective invasive diagnostic approach in patients undergoing ICA following coronary CTA (and CT-FFR) as compared to the traditional, “full ICA” approach. Our aim was to compare contrast volume and radiation dose used during ICA in both scenarios, seeking potential benefit for the patient in reducing those values by “diseased-vessel-only” approach. Results: Sensitivity, specificity, positive predictive value and negative predictive value of CTA in prediction of subsequent revascularization were 96%, 75%, 51% and 99%, respectively, and for CT-FFR 90%, 90%, 69% and 97%, respectively. Using CTA as a method to guide ICA would reduce contrast volume and estimated radiation dose (ED), by 35% and 42.0% respectively (P <0.0001 for both). Taking into consideration CT-FFR results, contrast volume would be reduced by 57% and ED by 69% (P <0.0001 for both). Conclusion: These real-world data support the concept that vessels with <50% diameter stenosis in QCT and hemodynamically insignificant in CTA-derived FFR may be skipped during ICA. Such approach would result in substantial reductions in contrast media volume used, as well as patient’s exposure to radiation during during ICA, while not leading to missed diagnoses

The platelet-to-lymphocyte ratio as a predictor of all-cause mortality in patients with coronary artery disease undergoing elective percutaneous coronary intervention and stent implantation

AbstractBackgroundThere is no data regarding the association between the platelet-to-lymphocyte ratio (PLR) and long-term mortality in patients with stable coronary artery disease (SCAD). The aim of this study is to evaluate the utility of the pre-procedural PLR for predicting long-term, all-cause mortality in patients with SCAD undergoing percutaneous coronary intervention (PCI) and stent implantation.MethodsWe analyzed a total of 2959 consecutive patients with SCAD who underwent PCI (balloon angioplasty followed by stent implantation or direct stenting) between July 2006 and December 2011 at our institution. The patients were stratified into tertiles according to their admission PLR. The association between the PLR value and the outcomes was assessed using Cox proportional regression analysis after adjusting for clinical angiographic and laboratory data.ResultsDuring median follow-up of 1124days, mortality was highest in patients with PLR within the 3rd tertile as compared to the 2nd and the 1st tertile (11.0% vs 8.7% vs. 9.6%, respectively, p=0.03). PLR remained associated with mortality in multivariable analysis including clinical variables, ejection fraction and angiographic parameters HR (per 10 units increase)=1.02 [95%CI,1.01÷1.04, p=0.006]. After adjustment for the eGFR and hemoglobin levels, PLR was however no longer significantly associated with mortality.ConclusionPLR has potential predictive value in patients with SCAD, which has not been reported previously, but statistical significance disappears after adjusting for estimated glomerular filtration rate (eGFR) and hemoglobin levels as a potential confounding variable

The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease

Associations of genotype with the Gensini score among patients without previous MI. (DOCX 14 kb

Temperature-dependent polymorphism of N-(4-fluorophenyl)-1,5-dimethyl-1H-imidazole-4-carboxamide 3-oxide: experimental and theoretical studies on intermolecular interactions in the crystal state

X-ray analysis of N-(4-fluorophenyl)-1,5-dimethyl-1H-imidazole-4-carboxamide 3-oxide reveals the temperature-dependent polymorphism associated with the crystallographic symmetry conversion. The observed crystal structure transformation corresponds to a symmetry reduction from I41 /a (I) to P43 (II) space groups. The phase transition mainly concerns the subtle but clearly noticeable reorganization of molecules in the crystal space, with the structure of individual molecules left almost unchanged. The Hirshfeld surface analysis shows that various intermolecular contacts play an important role in the crystal packing, revealing graphically the differences in spatial arrangements of the molecules in both polymorphs. The N-oxide oxygen atom acts as a formally negatively charged hydrogen bonding acceptor in intramolecular hydrogen bond of N–H…O− type. The combined crystallographic and theoretical DFT methods demonstrate that the observed intramolecular N-oxide N–H…O hydrogen bond should be classified as a very strong charge-assisted and closed-shell non-covalent interaction