A Sex-Specific Analysis of the Predictive Value of Troponin I and T in Patients With and Without Diabetes Mellitus After Successful Coronary Intervention

Background: Elevated levels of troponin are associated with future major adverse cardiac events (MACE). Data on the prognostic value of high sensitive troponin T (hs-TnT) compared to high sensitive troponin I (hs-TnI) in diabetic and non-diabetic patients are sparse.Methods: We analyzed patients of a single-center registry undergoing coronary stenting between 2003 and 2006. As a primary endpoint we assessed MACE, a composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke according to sex and diabetes status using log-rank. As a second endpoint, we assessed the prognostic impact of hs-TnT and hs-TnI on MACE, adjusting for known confounders using Cox regression analysis.Results: Out of 818 investigated patients, 267 (32.6%) were female. Diabetes mellitus type 2 (T2DM) was diagnosed in 206 (25.2%) patients.After a mean follow-up of 6.6 ± 3.7 years, MACE occurred in 235 (28.7%) patients. The primary endpoint components of cardiovascular death occurred in 115 (14.1%) patients, MI in 75 (9.2%), and ischemic stroke in 45 (5.5%). Outcomes differed significantly according to sex and diabetes status (p = 0.003). In descending order, MACE rates were as follows: female diabetic patients (40.8%), female non-diabetic patients (32.7%), male diabetic patients (28.9%), and male non-diabetic patients (24.8%). Additionally, females with diabetes were at higher risk of cardiovascular death compared to diabetic men (28 vs. 15%). Hs-TnI (HR 1.477 [95% CI 1.100–1.985]; p = 0.010) and hs-TnT (HR 1.615 [95%CI 1.111–2.348]; p = 0.012) above the 99th percentile were significantly associated with MACE. Both assays showed tendency toward association with MACE in all subgroups.Conclusion: Diabetic patients, particularly females, with known coronary artery disease had a higher risk of subsequent MACE. Both, hs-TnI and hs-TnT significantly correlated with MACE

Upstream Statin Therapy and Long-Term Recurrence of Atrial Fibrillation after Cardioversion: A Propensity-Matched Analysis

The relationship of statin therapy with recurrence of atrial fibrillation (AF) after cardioversion (CV) has been evaluated by several investigations, which provided conflicting results and particularly long-term data is scarce. We sought to examine whether upstream statin therapy is associated with long-term recurrence of AF after CV. This was a single-center registry study including consecutive AF patients (n = 454) undergoing CV. Cox regression models were performed to estimate AF recurrence comparing patients with and without statins. In addition, we performed a propensity score matched analysis with a 1:1 ratio. Statins were prescribed to 183 (40.3%) patients. After a median follow-up period of 373 (207–805) days, recurrence of AF was present in 150 (33.0%) patients. Patients receiving statins had a significantly lower rate of AF recurrence (log-rank p < 0.001). In univariate analysis, statin therapy was associated with a significantly reduced rate of AF recurrence (HR 0.333 (95% CI 0.225–0.493), p = 0.001), which remained significant after adjustment (HR 0.238 (95% CI 0.151–0.375), p < 0.001). After propensity score matching treatment with statins resulted in an absolute risk reduction of 27.5% for recurrent AF (21 (18.1%) vs. 53 (45.7%); p < 0.001). Statin therapy was associated with a reduced risk of long-term AF recurrence after successful cardioversion

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Phytochemical investigations and -glucosidase inhibitory activity of Caesalpinia pulcherrima (L.)

Das Enzym Glukosidase ist für die Spaltung von Polysacchariden in Glukose, welche resorbiert werden kann, verantwortlich. Wird das Enzym inaktiviert so verlangsamt sich die Glucoseaufnahme, weswegen Glukosidase Hemmer in der Therapie des Diabetes Typ 2 eingesetzt werden.(Mutschler, 2010)Diabetes ist ein wachsendes Problem der modernen Gesellschaft und die Anzahl der Betroffenen nimmt von Jahr zu Jahr zu. Um neue Therapie Ansätze zu finden wurde auf das Wissen der Traditionellen Thailändischen Medizin zurückgegriffen. Eine Studie fand heraus, dass die Blätter von Caesalpinia pulcherrima L., einer Pflanze die in der Traditionellen Thailändischen Medizin verwendet wird, dazu in der Lage sind das Enzym Glucosidase zu hemmen. Diese Entdeckung könnte zu neuen Diabetes Typ 2 Therapeutika führen. (Dej-adisai, 2015)Es wurden Extrakte mit Lösungsmittel unterschiedlicher Polarität hergestellt und auf ihre Glucosidase Hemmung untersucht. Das größte Potential wiesen der Ethanol (95.44 % Hemmung) und der Wasser Extrakt (53.6 % Hemmung) auf. (Prinz, 2015)In diesem Projekt wurde der Wasserextrakt der Blätter von Caesalpinia pulcherrima L. untersucht. Quercitrin, Myricitrin und Gallsäure konnten mittels Säulenchromatographie isoliert und mittels LC MS und NMR Spektroskopie identifiziert werden. Im nächsten Schritt wurde die Hemmung der Glucosidase bestimmt und mit der von Acarbose (IC50 = 0.306 mM, SE 0.06) verglichen. Das größte Potential wies Myricitrin ( IC50 von 1.21 mM, SE 0.07) auf gefolgt von Gallsäure (IC50 = 2.162, SE 0.17). Quercitrin war der schwächste Inhibitor (IC50 von 4.828 mM, SE 0.84). Zusammenfassend kann gesagt werden, dass die Ergebnisse dieser Untersuchung bestätigen, dass Caesalpinia pulcherrima L. zur Behanldung von Diabetes Typ 2 verwendet werden kann.The enzyme glucosidase is responsible for breaking up polysaccarides into single glucose molecules, which can be absorbed . The inhibiton of this enzyme leads to a reduced absorption of glucose and therefor glucosidase inhitiors are used to treat Diabetes Type 2. (Mutschler, 2010)Diabetes Type 2 is a growing problem in modern society, which affects more and more people each year. So, new ways of treatment are researched. The knowledge of Traditional Thai Medicine was consulted to find a new approach. The leaves of Caesalpinia pulcherrima L., a plant used in Traditional Thai Medicine, have shown potential in the inhibition of the activity of the enzyme glucosidase and might lead to the disvovery of a new anti diabetes drug in the future. (Dej-adisai, 2015)The leaves were extracted by solvents of different polarities and screened for their glucosidase inhibtory activity. The highest activity were shown by the ethanol and the water extract (95.4% and 53.6 % inhibition). (Prinz, 2015) In this project the water extract of Caesalpinia pulcherrima L. leaves was investigated. Quercitrin, myricitrin and gallic acid were isolated through column chromatography using different modes of isolation (adsoprtion and size exclusion) and identified by LC MS and NMR spectroscopy. They were subsequently tested for their glucosidase inhibitory activity and compared to that of acarbose (IC50 = 0.306 mM, SE 0.06). All three tested substances showed an inhibitory activity, but not as strong as acarbose. Myricitrin showed the best inhibition ( IC50 1.21 mM, SE 0.07), followed by gallic acid (IC50 2.162 mM, SE 0.17). The weakest inhibitor was quercitrin ( IC50 4.828 mM, SE 0.84). In conclusion, the findings of this project confirm the usefulness of Caesalpinia pulcherrima L. in the treatment of Diabetes Type 2.presented by Stephanie TscharreZusammenfassungen in Deutsch und EnglischKarl-Franzens-Universität Graz, Diplomarbeit, 2017(VLID)202022

Die Kommunikation von Kärntens KMU

Roland TscharreKlagenfurt, Alpen-Adria-Univ., Dipl.-Arb., 2009KB2009 07(VLID)241050

Uric acid, hyperuricemia and prognosis in acute myocardial infarction

Einleitung: Patienten mit akutem Koronarsyndrom weisen eine hohe Morbidität und Mortalität auf. Die Bestimmung des kardiovaskulären Risikos ist schwierig und teilweise unpräzise. Die Bestimmung neuer Marker und Risikofaktoren zur Verbesserung der Abschätzung des kardiovaskulären Risikoprofils sind notwendig. Harnsäure ist das Endprodukt des Purinstoffwechsels. Harnsäure und Hyperurikämie werden mit der Entwicklung von kardiovaskulären Risikofaktoren in Verbindung gebracht. Weiters haben experimentelle und klinische Studie einen Zusammenhang zw. Harnsäure mit endothelialer Dysfunktion, Inflammation und oxidativem Stress beschrieben. Ziel dieser Studie war die Bestimmung einer möglichen Assoziation von Harnsäure und Hyperurikämie mit der Langzeitprognose nach Herzinfarkt. Methodik: Wir haben den Einfluss von Harnsäure und Hyperurikämie auf kardiovaskuläre Ereignisse (engl. MACE) definiert als kardiovaskulärer Tod, Herzinfarkt und Schlaganfall mit Cox-Regression und „propensity-matching“ analysiert. Der additive prognostische Wert von Harnsäure wurde zusätzlich mittels „net reclassification improvement“ (NRI) Analysen bestimmt. Hyperurikämie wurde als Harnsäure > 6.0 mg/dl in Frauen, und > 7.0 mg/dl in Männern definiert. Ergebnisse: Insgesamt wurden 1215 Patienten eingeschlossen. Hyperurikämie war in 356 (29.3%) der Patienten nachweisbar. Die mittlere Nachbeobachtungszeit lag bei 5.5 2.9 Jahren. In den Cox-Regressionsanalysen waren Harnsäure (HR 1.091 [95%CI 1.035-1.150]; p<0.001) und das Vorhandensein von Hyperurikämie (HR 1.750 [95%CI 1.388-2.207]; p<0.001) signifikant mit dem Auftreten von MACE assoziiert. Die Ergebnisse zw. Cox-Regressionsanalyse und „propensity-matching“ waren vergleichbar. Hyperurikämie wies eine starke Korrelation mit zukünftiger kardiovaskulärer Mortalität (HR 1.606 [95%CI 1.157-2.228]; p<0.005) und für einen neuerlichen Herzinfarkt (HR 1.505 [95%CI 1.036-2.186]; p<0.032) auf. Hinsichtlich Schlaganfalls war keine Assoziation mit Hyperurikämie nachweisbar (HR 1.104 [95%CI 0.490-2.060]; p<0.970). Die prognostische Genauigkeit eines Risikomodels konnte durch die Hinzunahme von Harnsäure signifikant verbessert werden (kontinuierliche NRI p<0.004; kategorische NRI p<0.029; IDI p<0.002). Zusammenfassung: Harnsäure und Hyperurikämie wiesen einen signifikanten Zusammenhang mit MACE innerhalb von 5.5 Jahren auf und verbesserten die prognostische Genauigkeit eines Risikomodels. Unsere Resultate sind insofern bedeutend, als dass Hyperurikämie häufig vorkommt und Harnsäure therapeutisch gesenkt werden kann. Ob das Senken von Harnsäure einen prognostischen Benefit in Patienten mit Herzinfarkten bringt, muss in großen Interventionsstudien bestimmt werden.Introduction: Patients with acute coronary syndromes (ACS) still face a high-risk for subsequent adverse outcomes despite substantial advances in acute and long-term therapy.Estimating cardiovascular risk is challenging and risk assessment based on common cardiovascular risk factors still lacks precision. Novel risk factors or markers enabling more accurate cardiovascular risk profiling are necessary in order to enhance patient care and prognosis. Uric acid (UA) resembles the final protein of the purine nucleotide metabolism. Recent data have linked UA with the development of cardiovascular comorbidities. Moreover, experimental and clinical investigations demonstrated an independent association of UA with inflammatory processes, oxidative stress, and endothelial dysfunction. Considering the still remarkable number of adverse events after ACS, our specific intent was to investigate the relationship between UA and hyperuricemia with long-term prognosis in patients with ACS. Methods: We investigated the association of UA and hyperuricemia with composite MACE. MACE was defined as cardiovascular death, myocardial infarction (MI) or stroke. Cox regression analyses and propensity matching were used. Further, we investigated the influence of hyperuricemia particularly for cardiovascular death, MI, and stroke. A potential incremental predictive value of UA was determined by performing “net reclassification improvement” (NRI) analyses, and the “integrated discrimination improvement” (IDI). Hyperuricemia was defined as UA levels > 6.0 mg/dl in female patients, and > 7.0 mg/dl inmale patients. Results: For the final analysis, we included 1215 patients. Hyperuricemia was diagnosed in 356 (29.3%) patients. The mean follow-up period was 5.5 2.9 years. After multivariable adjustment, hyperuricemia HR 1.750 [95%CI 1.388-2.207]; p<0.001) and UA (HR 1.091 [95%CI 1.035-1.150]; p<0.001) were significantly associated with long-term MACE in Cox regression analysis. The results were similar between Cox regression analysis and propensity score matching. Hyperuricemia correlated with an elevated risk for cardiovascular death (HR 1.606 [95%CI 1.157-2.228]; p<0.005) and for MI (HR 1.505 [95%CI 1.036-2.186]; p<0.032), but only constituted a confounder for stroke (HR 1.104 [95%CI 0.490-2.060]; p<0.970). The prognostic accuracy of a risk prediction model (age, heart rate, systolic blood pressure, creatinine, cardiac biomarkers, Killip class, ST-segment deviation) increased significantly by the addition of UA (continuous NRI p<0.004; categorical NRI p<0.029; IDI p<0.002). Conclusion: UA and hyperuricemia were significantly associated with long-term MACE in ACS patients referred for PCI. Moreover, the addition of UA to a risk prediction model significantly increased its prognostic accuracy. These associations were independent ofcardiovascular comorbidities and other potential confounders. UA and hyperuricemia might be a helpful marker of cardiovascular risk in addition to established risk factors. UA is routinely assessed and represents a potentially treatable target. If pharmacological UA lowering in ischemic heart disease might be clinically beneficial remains to be investigated in large prospective clinical trials.Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersArbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüftMedizinische Universität Wien, Diss., 2020(VLID)495016

S1 Dataset_Contemporary use of P2Y12 in Austria_P ONE_Tscharre_et_al.sav

P2Y12-I in Austri

Pharmacist interventions to improve blood pressure control in primary care: a cluster randomised trial.

BACKGROUND High blood pressure (BP) is the single largest contributor to mortality world-wide. AIM To investigate the effectiveness of a pharmacists-led intervention to improve BP control using automated office blood pressure (AOBP). METHOD In this prospective parallel group, unblinded, cluster-randomised trial, 54 pharmacies enrolled pre-treated patients with uncontrolled AOBP above 135/85 mmHg. In the interventional group, pharmacists referred patients to the treating physician for therapy intensification in a structured fashion. In the control group, AOBP was recorded until the end of the trial. The primary endpoint was the proportion of patients achieving BP control at the threshold of 135/85 mmHg after 10 weeks. Key secondary endpoints were systolic AOBP reductions after 10 and 20 weeks. RESULTS A total of 497 patients were included between 2017 and 2019. In the interventional and control group, 61.5% and 19.8% of patients underwent a therapy modification within 20 weeks. The primary endpoint was achieved in 38.8% in the interventional group and 31.2% in the control group (mean difference 7.6%, 95% CI -8.1; 23.3, p = 0.336). Mean systolic AOBP reductions were greater in the interventional vs. control group at 10 and 20 weeks (14.3 ± 7.4 vs. 6.9 ± 7.0 mmHg, mean difference 7.3 mmHg, 95% CI 3.2;11.5, p < 0.001, and 15.5 ± 9.0 vs. 9.8 ± 7.5 mmHg, mean difference 5.8 mmHg, 95% CI 0.8;10.7, p = 0.023). Atrial fibrillation was newly detected in 7.8% of patients. CONCLUSION Through a pragmatic pharmacist-led disease management program, BP control was improved over time, without significant differences between groups. Greater systolic AOBP reductions were observed in the interventional vs. control group. (Pharmacists Intervention to Improve Hypertension Management in Primary Care:APOTHECARE; ClinicalTrials.gov registration NCT03274531)

Growth Differentiation Factor 15 Is Associated with Platelet Reactivity in Patients with Acute Coronary Syndrome

Bleeding events in patients with acute coronary syndrome (ACS) are a risk factor for adverse outcomes, including mortality. We investigated the association of growth differentiation factor (GDF)-15, an established predictor of bleeding complications, with on-treatment platelet reactivity in ACS patients undergoing coronary stenting receiving prasugrel or ticagrelor. Platelet aggregation was measured by multiple electrode aggregometry (MEA) in response to adenosine diphosphate (ADP), arachidonic acid (AA), thrombin receptor-activating peptide (TRAP, a protease-activated receptor-1 (PAR-1) agonist), AYPGKF (a PAR-4 agonist) and collagen (COL). GDF-15 levels were measured using a commercially available assay. GDF-15 correlated inversely with MEA ADP (r = −0.202, p = 0.004), MEA AA (r = −0.139, p = 0.048) and MEA TRAP (r = −0.190, p = 0.007). After adjustment, GDF-15 was significantly associated with MEA TRAP (β = −0.150, p = 0.044), whereas no significant associations were detectable for the other agonists. Patients with low platelet reactivity in response to ADP had significantly higher GDF-15 levels (p = 0.005). In conclusion, GDF-15 is inversely associated with TRAP-inducible platelet aggregation in ACS patients treated with state-of-the-art antiplatelet therapy and significantly elevated in patients with low platelet reactivity in response to ADP