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The HeartMate 3 (HM3) left ventricular assist device has decreased thromboembolic events and minimized the risk of pump thrombosis. However, bleeding complications due to combined antithrombotic therapy with a vitamin K antagonist (VKA) and aspirin remain high. Only limited data on the safety of VKA monotherapy in HM3 patients are available. A systematic search on the main databases was performed. Observational data and randomized trials were eligible for this analysis. As primary endpoint, we analyzed hemocompatibility-related adverse events (HRAE). As secondary endpoints, we investigated the individual components of the primary endpoint. The analysis was carried out using the odds ratio (OR) as outcome measure. A random-effects model was fitted to the data. Five manuscripts fulfilled the inclusion criteria. These trials included 785 patients (381 on VKA monotherapy, 404 on VKA and aspirin). VKA monotherapy significantly reduced HRAE (OR: 0.11 [95% confidence interval {CI}: 0.02-0.59], p = 0.01, I2 = 87%). The reduction was driven by a decrease in bleeding complications (OR: 0.12 [95% CI: 0.02-0.62], p = 0.01, I2 = 86%) without increasing the rates of thromboembolic events (OR: 0.69 [95% CI: 0.26-1.81], p = 0.45, I = 0%). Vitamin K antagonist monotherapy is associated with a significant reduction of bleeding events without increasing the risk of thromboembolic complications in HM3 patients., Competing Interests: Disclosure: T.S. received consulting/advisory fees from Medtronic Inc., Abbott Inc., BiVACOR, Berlin Heart, and CorWave; and received grant support from Medtronic Inc., Abbott Inc., Berlin Heart, and CorWave. D.W. is a proctor for Abbott Inc. and received consulting/advisory fees from Abbott Inc. and Xenios/Fresenius Medical Care. D.Z. is a proctor for and received speaker/consulting fees from Medtronic Inc., Abbott Inc., Berlin Heart, Edwards, Abiomed, and grant support from Medtronic Inc. and Abbott Inc. T.G. received speaker/consulting fees from AstraZeneca, Amgen, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Daiichi- Sankyo, Novartis, and Pfizer, and grant support from Boehringer-Ingelheim, Bristol Myers Squibb, Medtronic and Abbott. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Background: Patients with left ventricular assist devices (LVADs) are treated with a potent antithrombotic regimen to prevent pump thrombosis and thromboembolism. High on-treatment residual platelet reactivity (HRPR) is associated with ischemic outcomes in cardiovascular disease., Objectives: In the current study, we investigated the prevalence and clinical impact of HRPR in stable LVAD patients., Methods: Pump thrombosis, bleeding events, and death were assessed in 62 LVAD patients (19 HeartWare HVAD [Medtronic] and 43 HeartMate 3 [Abbott]) during a 2-year follow-up. Platelet aggregation was measured by multiple electrode aggregometry, and HRPR was defined as arachidonic acid (AA)-inducible platelet aggregation of ≥21 aggregation units. Soluble P-selectin was determined by enzyme-linked immunosorbent assay., Results: Three patients (4.8%) had pump thrombosis and 10 patients (16.1%) suffered a bleeding complication. AA-inducible platelet aggregation was significantly higher in patients with pump thrombosis ( P  = .01), whereas platelet aggregation in response to adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP) was comparable between patients without and those with pump thrombosis (both P > .05). Platelet aggregation in response to AA, ADP, and TRAP was similar in patients without and with a bleeding event (all P > .05). HRPR was detected in 29 patients (46.8%) and was associated with significantly higher platelet aggregation in response to AA, ADP, and TRAP as well as higher levels of soluble P-selectin compared with patients without HRPR (all P  < .05). All pump thromboses occurred in patients with HRPR (3 vs 0; P  = .06) and HVAD., Conclusion: Platelet reactivity is associated with pump thrombosis in LVAD patients. HRPR may represent a risk marker for pump thrombosis, particularly in HVAD patients., (© 2024 The Author(s).)

Background: Participation in ultra-endurance races may lead to a transient decline in cardiac function and increased cardiovascular biomarkers. This study aims to assess alterations in biventricular function immediately and five days after the competition in relation to elevation of high-sensitivity cardiac Troponin I (hs-cTnI) and N-terminal-pro-brain-natriuretic-peptide (NT-proBNP)., Methods and Results: Fifteen participants of an ultramarathon (UM) with a running distance of 130 km were included. Transthoracic echocardiography and quantification of biomarkers was performed before, immediately after and five days after the race. A significant reduction in right ventricular fractional area change (FAC) was observed after the race (48.0 ± 4.6% vs. 46.7 ± 3.8%, p = 0.011) that persisted five days later (48.0 ± 4.6% vs. 46.3 ± 3.9%, p = 0.027). No difference in left ventricular ejection fraction (LVEF) was found (p = 0.510). Upon stratification according to biomarkers, participants with NT-proBNP above the median had a significantly reduced LVEF directly (60.8 ± 3.6% vs. 56.9 ± 4.8%, p = 0.030) and five days after the race (60.8 ± 3.6% vs. 55.3 ± 4.5%, p = 0.007) compared to baseline values. FAC was significantly reduced five days after the race (48.4 ± 5.1 vs. 44.3 ± 3.9, p = 0.044). Athletes with hs-cTnI above the median had a significantly reduced FAC directly after the race (48.1 ± 4.6 vs. 46.5 ± 4.4, p = 0.038), while no difference in LVEF was observed. No alteration in cardiac function was observed if hs-cTnI or NT-proBNP was below the median., Conclusion: A slight decline in cardiac function after prolonged strenuous exercise was observed in athletes with an elevation of hs-cTnI and NT-proBNP above the median but not below., (© 2024. The Author(s).)

Background: Only small randomized trials have investigated the efficacy and safety of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) and end-stage kidney disease., Objectives: To perform a systematic review and meta-analysis comparing anticoagulation with DOACs to VKAs in patients with NVAF undergoing chronic hemodialysis., Methods: A systematic search using Medline, Web of Science, and Embase was performed. All randomized trials comparing DOACs with VKAs in patients with NVAF undergoing chronic hemodialysis were included. As primary endpoint, we analyzed all-cause mortality. As secondary endpoints, we investigated total bleeding events, life-threatening or major bleeding events, and thromboembolic events or stroke. We used the odds ratio as outcome measure and fitted a random-effects model due to the expected heterogeneity., Results: Three studies fulfilled the inclusion criteria comprising 383 patients (218 on apixaban or rivaroxaban, 165 on VKA). No significant difference between DOACs and VKAs regarding death (OR, 0.94; 95% CI, 0.55-1.63; p = .84), total bleedings (OR, 0.99; 95% CI, 0.63-1.54; p = .96) and life-threatening or major bleeding (OR, 0.65; 95% CI, 0.32-1.33, p = .24) was detected. There was a trend toward a reduction of thromboembolic events or stroke in patients receiving DOACs (OR, 0.39; 95% CI, 0.14-1.05; p = .06)., Conclusion: Orally administered activated factor X inhibitors carried a similar risk of bleeding and death when compared with VKAs in patients with NVAF undergoing chronic hemodialysis. Moreover, there was a trend towards a reduction of thromboembolic events or stroke in patients receiving DOACs., (© 2024 The Author(s).)

Background and Aims: It is suggested that the changes in atherosclerosis happen mainly under the influence of non-fasting lipids. To date, the studies in the postprandial state were primarily performed on healthy subjects. This exploratory, cross-sectional study investigates the change in lipid profile, inflammation, and platelet activation in patients with different cardiovascular risk profiles in the postprandial state., Methods: The studied population consists of 66 patients with different cardiovascular risks: patients with a history of the chronic coronary syndrome (CCS) and diabetes mellitus type 2 (DM2) (n = 20), CCS without DM2 (n = 25), and a healthy control group (n = 21). Lipid variables and markers of platelet function and inflammation were assessed during the fasting state and three and 5 h after a standardized fat meal using a standardized oral fat tolerance test (OFTT), a milkshake with 90 g of fat., Results: Patients with CCS and DM2 were significantly older and had the highest BMI. All patients with CCS were on acetylsalicylic acid, and 95% of CCS patients were on high-dose statins. The absolute leukocyte and neutrophile count increased significantly in the control group during the OFTT in comparison to CCS subjects. There was a significant decrease of HDL and increase of triglycerides during the OFTT, however with no difference between groups. There was no difference in the change of platelet activity between all groups., Conclusion: This study showed that OFTT leads to an increased postprandial inflammation response in healthy group compared to CCS ± DM2 while there was no change in lipid profile and platelet activity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Aims: Reduction of low-density lipoprotein cholesterol (LDL-C) decreases cardiovascular mortality and morbidity. Bempedoic acid represents a promising novel lipid-modifying agent for patients who cannot reach guideline recommended LDL-C goals or statin-intolerant patients, but data on safety and cardiovascular outcomes are limited. We therefore aimed to systematically review randomized controlled trials investigating bempedoic acid vs. placebo in patients with hyperlipidaemia., Methods: A systematic search on the databases PubMed, Web of Science, and Embase until 20 March 2023 was performed. All randomized trials comparing bempedoic acid (180 mg daily) with placebo in patients with an indication for lipid-lowering therapy were included. As a primary endpoint, we analysed three-point major adverse cardiovascular events (MACEs) consisting of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. The analysis was carried out using the odds ratio (OR) as the outcome measure. Due to the expected heterogeneity across studies, a random-effects model was fitted to the data., Results: Out of 258 manuscripts, 10 manuscripts fulfilled the inclusion criteria. In total, these trials included 18 200 patients (9765 on bempedoic acid, 8435 on placebo). Bempedoic acid significantly reduced MACEs compared with placebo (OR 0.84 [95% confidence interval (CI) 0.76-0.96]; P < 0.001; I2 = 0%). The endpoint reduction was driven by a lower rate of non-fatal MI, whereas bempedoic acid had no significant effect on stroke (OR 0.86 [95% CI 0.69-1.08]; P = 0.20, I2 = 0%) and all-cause mortality (OR 1.19 [95% CI 0.73-1.93]; P = 0.49; I2 = 18%)., Conclusion: Bempedoic acid reduced non-fatal MI in patients with hyperlipidaemia, whereas it had no significant effect on stroke and all-cause mortality., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Cardiovascular disease, particularly coronary artery disease (CAD), remains the leading cause of mortality and morbidity in industrialized countries. Platelet activation and aggregation at the site of endothelial injury play a key role in the processes ultimately resulting in thrombus formation with vessel occlusion and subsequent end-organ damage. Consequently, antiplatelet therapy has become a mainstay in the pharmacological treatment of CAD. Several drug classes have been developed over the last decades and a broad armamentarium of antiplatelet agents is currently available. This review portrays the evolution of antiplatelet therapy, and provides an overview on previous and current antiplatelet drugs and strategies., Competing Interests: None declared., (Thieme. All rights reserved.)

Background:  The ABO blood group system is linked to hemostasis via its relationship with von Willebrand factor (VWF) and factor VIII (FVIII). In the current study, we investigated the association of the ABO system with clinical outcomes as well as VWF and platelet function in patients with left ventricular assist devices (LVADs)., Methods:  Bleeding and thromboembolic complications were assessed in 111 patients during 1 year after LVAD implantation. In 67 LVAD patients, VWF antigen, VWF activity, VWF ristocetin cofactor, VWF collagen-binding, and FVIII activity were assessed. Platelet surface P-selectin and activated glycoprotein IIb/IIIa were determined by flow cytometry, and soluble P-selectin was measured with an enzyme-linked immunoassay. Platelet aggregation was assessed by light transmission and impedance aggregometry., Results:  Thirty-six patients (32.4%) experienced a bleeding and 22 patients (19.8%) a thromboembolic event. In univariate analyses, patients with blood group O had numerically more bleeding complications and less thromboembolic events as compared to patients with blood group non-O (both p ≥ 0.05). After multivariable adjustment, blood group O was significantly associated with a higher risk of bleeding (hazard ratio 2.42 [95% confidence interval 1.03-5.70], p  = 0.044) but not linked to thromboembolic complications., Conclusion:  Patients with blood group O had significantly lower levels of VWF and FVIII (all p  < 0.05), whereas P-selectin expression in response to thrombin-receptor activating peptide and soluble P-selectin were higher as compared to patients with blood group non-O (both p  < 0.05). LVAD patients with blood group O are at an increased bleeding risk, potentially due to lower VWF and FVIII levels., Competing Interests: T.S. received research grants from Abbott, CorWave, and Medtronic, and is a consultant for Abbott and Medtronic. D.W. is a consultant and proctor for Abbott and Medtronic. D.Z. received research grants from Abbott and Medtronic, is an advisory board member for Abbott, Medtronic, and Berlin Heart, and is a proctor for Abbott and Medtronic. T.G. received research grants from Boehringer-Ingelheim, Bristol Myers Squibb, Medtronic, and Abbott, and lecture fees from Amgen, Boehringer-Ingelheim, Bayer, Bristol Myers Squibb, Vifor, Daiichi Sankyo, Pfizer, and Novartis. The other authors have no relevant conflicts of interest to declare., (Thieme. All rights reserved.)

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.

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)., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Growth differentiation factor (GDF)-15 inhibits platelet activation, prevents thrombus formation, and has been linked to bleeding events. This was a prospective study including 51 left-ventricular assist device (LVAD) patients on aspirin and phenprocoumon. Platelet surface expression of activated glycoprotein (GP) IIb/IIIa was assessed by flow cytometry, and platelet aggregation was measured by multiple electrode aggregometry (MEA) in response to arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor-activating peptide (TRAP), a protease-activated-receptor-1 (PAR-1) agonist. GDF-15 was determined with a commercially-available assay. There was a trend towards an inverse correlation of GDF-15 with activated GPIIb/IIIa in response to TRAP (r = -0.275, p = 0.0532) but not in response to AA and ADP. Moreover, GDF-15 correlated with MEA TRAP (r = -0.326, p = 0.0194), whereas it did not correlate with MEA ADP and MEA AA. In a second step, GDF-15 levels in the fourth quartile were defined as high GDF-15. Patients with high GDF-15 showed significantly lower TRAP-inducible platelet aggregation by MEA compared to patients in the first quartile (63 AU vs. 113 AU, p = 0.0065). In conclusion, in LVAD patients receiving state-of-the-art antithrombotic therapy, GDF-15 correlates inversely with residual platelet reactivity via PAR-1.

Background: Neurotensin is involved in fatty acid and glucose metabolism and promotes the development of obesity and diabetes. These associations appear to be more pronounced in women. We investigated the association of neurotensin with long-term major adverse cardiovascular events (MACE) in patients presenting with acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI)., Methods: We included 452 consecutive patients [144 (31.9%) females] undergoing PCI for ACS or CCS. Plasma samples drawn after PCI were analyzed for neurotensin with an enzyme-linked immunoassay. As primary endpoint, a composite of MACE including all-cause death, non-fatal myocardial infarction and non-fatal stroke during 7 years of follow-up was investigated. As secondary endpoint, we investigated all-cause death., Results: Neurotensin levels did not differ between male and female patients ( p = 0.560). MACE occurred in 150 (33.2%) patients. Restricted cubic splines demonstrated a U-shaped association of log-transformed neurotensin with the primary and secondary endpoint. Therefore, we dichotomized our cohort according to tertiles of log-transformed neurotensin. In Kaplan-Meier analysis including the total cohort and restricted to male patients log- neurotensin tertiles were not associated with MACE (both p > 0.05). Moreover, in the overall cohort and in male patients multivariable Cox regression analysis log-neurotensin tertiles were not associated with MACE or with all-cause death (all p > 0.05). However, in female patients log-neurotensin was associated with MACE in Kaplan-Meier analysis (log-rank p = 0.013). Also, after multivariable adjustment female patients in the first tertile had a significantly increased risk for MACE compared to female patients in the second tertile [HR 3.84 (95% CI 1.71-8.60), p = 0.001]. There was tendency for increased risk in female patients in the third tertile compared to the second tertile [HR 2.14 (95% CI 0.97-4.73), p = 0.058]. Moreover, in female patients the [first and the third tertile of log- neurotensin were associated with all-cause death 1s vs. 2nd tertile: HR 3.03 (95% CI 1.21-7.63), p = 0.018; 3rd vs. 2nd tertile: HR 3.01 (95% CI 1.22-7.44), p = 0.016]., Conclusion: In female patients with CAD undergoing PCI, neurotensin has a U-shaped relationship with adverse outcomes. These data suggest a sex specific association between neurotensin and long-term adverse events after PCI., Competing Interests: AK-W was employed by the Gender Institute, Lapura Women's Health Resort, Gars am Kamp, Austria. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tscharre, Farhan, Freynhofer, Leutner, Baumgartner-Parzer, Tentzeris, Vogel, Tinhofer, Rohla, Weiss, Huber and Kautzky-Willer.)

Left-ventricular assist devices (LVADs) improve outcomes in end-stage heart failure patients. Two centrifugal-flow LVAD systems are currently approved, HeartMate 3 (HM3) and Medtronic/Heartware HVAD (HVAD). Clinical findings suggest differences in thrombogenicity between both systems. We compared markers of platelet activation and aggregation between HM3 and HVAD. We prospectively included 59 LVAD patients (40 HM3, 19 HVAD). Platelet P -selectin expression, activated glycoprotein (GP) IIb/IIIa and monocyte-platelet aggregates (MPA) were assessed by flow-cytometry. Platelet aggregation was measured by light-transmission aggregometry (LTA) and multiple-electrode aggregometry (MEA). Von-Willebrand factor (VWF) antigen (VWF:Ag), VWF activity (VWF:Ac), and VWF multimer pattern analysis were determined. Soluble P -selectin (sP-selectin) was measured with an enzyme-linked immunoassay. P -selectin, GPIIb/IIIa and MPA levels in vivo and in response to arachidonic acid, adenosine diphosphate, and thrombin receptor activating peptide were similar between HM3 and HVAD (all p > .05). Likewise, agonist-inducible platelet aggregation by LTA and MEA did not differ between HM3 and HVAD (all p > .05). VWF:Ag levels and FVIII:C were similar between both systems (both p > .05), but patients with HVAD had significantly lower VWF:Ac ( p = .011) and reduced large VWF multimers ( p = .013). Finally, sP-selectin levels were similar in patients with HVAD and HM3 ( p = .845). In conclusion, on-treatment platelet activation and aggregation are similar in HM3 and HVAD patients. Potential clinical implications of observed differences in VWF profiles between both LVAD systems need to be addressed in future clinical trials.

A high platelet-to-lymphocyte ratio (PLR) has recently been associated with ischemic outcomes in cardiovascular disease. Increased platelet reactivity and leukocyte-platelet aggregate formation are directly involved in the progress of atherosclerosis and have been linked to ischemic events following percutaneous coronary intervention (PCI). In order to understand the relation of PLR with platelet reactivity, we assessed PLR as well as agonist-inducible platelet aggregation and neutrophil-platelet aggregate (NPA) formation in 182 acute coronary syndrome (ACS) patients on dual antiplatelet therapy with aspirin and prasugrel (n = 96) or ticagrelor (n = 86) 3 days after PCI. PLR was calculated from the blood count. Platelet aggregation was measured by multiple electrode aggregometry and NPA formation was determined by flow cytometry, both in response to ADP and SFLLRN. A PLR ≥91 was considered as high PLR based on previous data showing an association of this threshold with adverse ischemic outcomes. In the overall cohort and in prasugrel-treated patients, high PLR was associated with higher SFLLRN-inducible platelet aggregation (67 AU [50-85 AU] vs 59.5 AU [44.3-71.3 AU], P = .01, and 73 AU [50-85 AU] vs 61.5 AU [46-69 AU], P = .02, respectively). Further, prasugrel-treated patients with high PLR exhibited higher ADP- (15% [11%-23%] vs 10.9% [7.6%-15.9%], P = .007) and SFLLRN-inducible NPA formation (64.3% [55.4%-73.8%] vs 53.8% [44.1%-70.1%], P = .01) as compared to patients with low PLR. These differences were not seen in ticagrelor-treated patients. In conclusion, high PLR is associated with increased on-treatment platelet reactivity in prasugrel-treated patients, but not in patients on ticagrelor.

Background and Aims: Protease-activated receptor (PAR)-1-mediated platelet activation may vary according to sex and clinical situation. In order to investigate sex-specific platelet activation through PAR-1, we assessed platelet response to thrombin receptor-activating peptide (TRAP) in 562 patients undergoing cardiac catheterization without (Group 1A) and with (Group 1B) acute coronary syndrome (ACS). Subsequently, we sought to confirm our findings in 287 patients undergoing elective (Group 2A) or acute (Group 2B) percutaneous coronary intervention., Methods: TRAP-stimulated platelet surface expression of P-selectin and activated glycoprotein IIb/IIIa (GPIIb/IIIa) were measured by flow cytometry in Group 1. Light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) in response to TRAP were assessed in Group 2., Results: In Group 1A, platelet activation in response to TRAP was significantly higher in women compared to men (P-selectin: 511 MFI [443-597 MFI] vs. 471 MFI [393-552 MFI]; GPIIb/IIIa: 84 MFI [58-119 MFI] vs. 70 MFI [47-103 MFI]; both p ≤ 0.002). In contrast, in Group 1B, TRAP-stimulated P-selectin and activated GPIIb/IIIa were similar in men and women (both p ≥ 0.3). Likewise, TRAP-stimulated platelet aggregation was significantly higher in female patients in Group 2A (LTA: 66% [54-76%] vs. 51% [41-65%]; MEA: 78 AU [66-107 AU] vs. 62 AU [52-88 AU]; both p ≤ 0.02), whereas men and women in Group 2 B had similar platelet aggregation (p = 0.5). The occurrence of ischemic endpoints did not differ significantly between men and women in Group 1A and Group 1B., Conclusions: Platelet PAR-1 signaling is more pronounced in women than in men without ACS. In ACS, however, PAR-1-mediated platelet activation is similar in male and female patients., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: In patients with acute coronary syndrome (ACS), angiotensin-converting enzyme (ACE) inhibitors are preferred over angiotensin receptor blockers (ARBs). However, in a recent pilot study, treatment with ACE inhibitors was associated with increased platelet reactivity compared to ARBs. Therefore, we sought to investigate the impact of renin-angiotensin-aldosterone system (RAAS) blockade with ACE inhibitors and ARBs on platelet aggregation in patients with ACS undergoing percutaneous coronary intervention., Methods: On-treatment residual platelet reactivity in response to arachidonic acid (AA), adenosine diphosphate (ADP), SFLLRN, AYPGKF, and collagen was assessed by multiple electrode aggregometry (MEA) in 197 ACS patients on dual antiplatelet therapy (DAPT) with aspirin and either prasugrel or ticagrelor., Results: One hundred sixty-five (83.7%) patients were treated with ACE inhibitors, 32 (16.3%) with ARBs. On-treatment residual AA- and ADP-inducible platelet reactivity was significantly higher in patients with ACE inhibitors (both p < 0.05). Likewise, SFLLRN was significantly higher in patients with ACE inhibitors (p = 0.036) and there was a trend for higher AYPGKF- and collagen-inducible platelet reactivity (p = 0.053 and p = 0.082). The incidence of high on-treatment residual platelet reactivity AA was significantly higher in patients with ACE inhibitors (52 [31.5%] vs. 3 [9.4%] patients; p = 0.019)., Conclusion: ACE inhibitors are associated with increased on-treatment residual platelet reactivity in ACS patients with potent DAPT. Further clinical trials are needed to elucidate the role of RAAS blockade with ACE inhibitors and ARBs in ACS patients treated according to current standards., (© 2020. The Author(s).)

The physiological response to high-level endurance exercise, such as running a marathon, poses several beneficial but also potentially harmful metabolic changes. The objective of this study was to determine the impact of marathon (M) and ultra-marathon (UM) on inflammation and iron homeostasis in paired samples. Fifteen well-trained, non-professional endurance athletes (14 males, 1 female) performed both a 130 km ultra-marathon and a traditional 42.195 km marathon. We determined markers of inflammation and iron homeostasis before, immediately after, and within 5 days after finishing each run, respectively. Biomarkers of inflammation (leucocytes, neutrophil granulocytes, monocytes, and c-reactive protein [CRP]) increased significantly after both marathon and ultra-marathon with higher levels of CRP after ultra-marathon compared with marathon both immediately after the race (18.15 ± 12.41 vs 5.58 ± 9.65 mg/L, P < .001) and at follow-up (15.67 ± 16.97 vs 7.19 ± 7.75 mg/L, P = .045) Concentrations of ferritin also increased significantly after both races and remained high at follow-up. Higher levels of ferritin immediately after the race (111.5 ± 103.2 vs 84.8 ± 86.3, P = .001) and at follow-up (102.7 ± 79.5 vs 74.6 ± 65.6, P = .001) were found in ultra-marathon finishers. The observed increase of serum iron and transferrin saturation (TSAT) after marathon and the decrease of serum iron and TSAT after ultra-marathon resulted in a significant absolute difference between the two races. The present data suggest a higher degree of inflammation after ultra-marathon compared with marathon. Markers of iron homeostasis also showed different response patterns with regard to running distance., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

Structural aspects of red blood cells have been associated with cardiovascular disease. No data linking mean corpuscular volume (MCV) to clinical outcomes and on-treatment platelet reactivity in patients with peripheral artery disease (PAD) are available. We investigated a composite of atherothrombotic events and target vessel restenosis or reocclusion following infrainguinal stenting for stable PAD. Residual platelet reactivity was measured by light transmission aggregometry (LTA) and the VerifyNow assays. We included 104 patients receiving dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. In receiver-operating characteristic analysis, MCV effectively discriminated between patients with and without adverse outcomes and identified a MCV ≤90.8 fL as optimal cutoff. Adverse outcomes occurred significantly more often in patients with low MCV (log-rank P = .002). In univariable Cox regression analysis, low MCV was associated with an increased risk of future adverse outcomes (hazard ratio [HR]: 2.662 [95%CI: 1.304-5.434]; P = .007) and remained significantly associated after adjustment (HR: 2.591 [95%CI: 1.242-5.403]; P = .011). Mean corpuscular volume was inversely correlated with arachidonic acid (AA)- and adenosine diphosphate (ADP)-inducible platelet reactivity by LTA and with the VerifyNow aspirin assay. Low MCV is associated with adverse outcomes over 2 years following infrainguinal stenting. Mean corpuscular volume correlates inversely with AA- and ADP-inducible platelet reactivity during DAPT.

Background: Von Willebrand factor (VWF) and its cleaving protease a disintegrin-like and metalloprotease with thrombospondin type I repeats 13 (ADAMTS13) are pivotal mediators of thrombosis and are associated with the progression of atherosclerosis. We investigated the impact of VWF, ADAMTS13 and VWF/ADAMTS13 on long-term major adverse cardiovascular outcomes (MACE) in patients undergoing percutaneous coronary intervention (PCI)., Methods: We analysed 701 patients undergoing PCI between 2003 and 2006. VWF and ADAMTS13 antigen levels were measured before PCI. As primary endpoint, we investigated MACE, a composite of all-cause mortality, myocardial infarction or ischemic stroke during 8 years of follow-up. As secondary endpoint, we investigated all-cause mortality., Results: Mean age was 63.8 years, 496 (70.8%) were male. Acute coronary syndrome (ACS) was diagnosed in 347 (49.5%) patients, stable coronary artery disease (SCAD) in 354 (50.5%). During follow-up 228 (32.5%) patients experienced MACE, and 161 (23.0%) died. In ACS patients, VWF was significantly associated with MACE (HR 1.402 (95%CI 1.003-1.959), p = 0.048), whereas ADAMTS13 and VWF/ADAMTS13 had no predictive value. In SCAD, neither VWF, ADAMTS13, nor VWF/ADAMTS13 correlated with MACE. VWF was significantly associated with all-cause death in ACS patients (HR 1.841 (95%CI 1.187-2.856), p = 0.006), but not in SCAD (1.394 (95%CI 0.856-2.269), p = 0.181). ADAMTS13 and VWF/ADAMTS13 were not correlated with ACS and SCAD, respectively., Conclusion: VWF but not ADAMTS13 and VWF/ADAMTS13 was associated with MACE and mortality in patients with ACS but not SCAD. This finding highlights the importance of VWF as an essential marker of risk in patients with ACS., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: An elevation of cardiac biomarkers is observed after intense or long-lasting physical activity. However, a recent meta-analysis has suggested that there might be an inverse relationship between duration of exercise and degree of biomarker elevation. The objective of this observational study was to investigate the impact of ultra-marathon (UM) vs. marathon (M) on biomarkers of myocyte necrosis and hemodynamic stress/congestion., Methods: Well-trained endurance athletes were recruited to participate in a 130-km UM and a M run. Troponin I (TnI), creatine kinase (CK), N-terminal pro-brain natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), and copeptin were measured after both events, respectively., Results: Fifteen athletes (14 males, one female) were included. There was no difference in exercise intensity according to the Borg scale (UM 16 [IQR 15-17], M 16 [IQR 14-17]; p = 0.424). Biomarkers of myocyte necrosis both differed significantly with higher levels of TnI (UM 0.056 ng/L [IQR 0.022-0.104), M 0.028 ng/L [IQR 0.022-0.049]; p = 0.016) and CK (UM 6992 U/l [IQR 2886-23038], M 425 U/l [IQR 327-681]; p = 0.001) after UM compared to M. Also, NT-proBNP (UM 723 ng/L [IQR 378-1152], M 132 ng/L [IQR 64-198]; p = 0.001) and MR-proADM (UM 1.012 nmol/L [IQR 0.753-0.975], M 0.877 nmol/L [IQR 0.550-0.985]; p = 0.023) as markers of myocardial congestion were significantly higher after UM. There was a tendency for elevated copeptin levels after M, but did not reach statistical significance (p = 0.078)., Conclusion: Ultra-marathon is associated with higher levels of biomarkers of myocyte necrosis and cardiac congestion compared to marathon, highlighting the impact of exercise duration on the cardiovascular system.

Antiplatelet therapy reduces atherothrombotic risk and has therefore become a cornerstone in the treatment of cardiovascular disease. Aspirin, adenosine diphosphate P2Y 12 receptor antagonists, glycoprotein IIb/IIIa inhibitors, and the thrombin receptor blocker vorapaxar are effective antiplatelet agents but significantly increase the risk of bleeding. Moreover, atherothrombotic events still impair the prognosis of many patients with cardiovascular disease despite established antiplatelet therapy. Over the last years, advances in the understanding of thrombus formation and hemostasis led to the discovery of various new receptors and signaling pathways of platelet activation. As a consequence, many new antiplatelet agents with high antithrombotic efficacy and supposedly only moderate effects on regular hemostasis have been developed and yielded promising results in preclinical and early clinical studies. Although their long journey from animal studies to randomized clinical trials and finally administration in daily clinical routine has just begun, some of the new agents may in the future become meaningful additions to the pharmacological armamentarium in cardiovascular disease.

Background: Increased platelet turnover and high platelet reactivity are associated with short-term major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) or stable coronary artery disease (SCAD). We investigated the impact of platelet turnover on long-term MACE., Methods: Consecutive patients presenting with ACS or SCAD undergoing PCI between 2009 and 2010 were included. All patients received clopidogrel and aspirin as dual antithrombotic therapy regimen. Multivariable Cox proportional hazard models were applied to assess the prognostic impact of platelet turnover (reticulated platelet count [RPC], mean platelet volume [MPV]) and function on long-term MACE, a composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke., Results: In total, 477 patients were eligible. Mean age was 64.3 ± 12.7 years, 68.8% were male. Median follow-up was 5.8 (IQR 4.2-6.5) years. Median RPC was 7.6 (IQR 5.6-10.4) g/L and median MPV was 10.7 (IQR 10.1-11.3) fL. In univariable analysis, RPC was associated with MACE, both as continuous (HR 1.064 [95%CI 1.021-1.111]; P = .006) and dichotomized (HR 1.693 [95%CI 1.156-2.481]; P = .006) variable. After adjustment, continuous RPC (HR 1.055 [95%CI 1.012-1.099]; P = .010) and dichotomized RPC (HR 1.716 [95%CI 1.152-2.559]; P = .007) remained significantly associated with MACE. Neither MPV nor platelet function testing was associated with long-term adverse outcome., Conclusion: Increased platelet turnover is associated with long-term adverse outcome in patients with coronary artery disease undergoing PCI. Platelet turnover represents a new marker of atherothrombotic risk and might help to guide composition or duration of antiplatelet therapy., (© 2019 Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: Classifying myocardial infarction into type 1 (T1MI) or type 2 (T2MI) remains a challenge in clinical practice. We aimed to identify factors contributing to variation in the classifications of MI into type 1 or type 2. In addition, pooled analyses of long-term mortality and reinfarction outcomes were performed., Methods: We searched Medline, Embase and Web of Science through January 2018 for observational studies or clinical trials classifying patients as either T1MI or T2MI. Studies with baseline characteristics allowing a comparison between both groups were included. Inverse variance random-effects models were used to pool risk ratios (RR)., Results: Overall, 93,194 patients from 20 included observational studies were classified as T1MI and 9291 as T2MI; corresponding to 87.9% and 8.8% of all patients diagnosed with MI. Inclusion of ST-elevation MI patients was inconsistent among studies. Coronary angiography was performed in 77.7% and 31.5% of all patients with T1MI and T2MI, respectively. From a subgroup of 11 studies, percutaneous coronary intervention was performed in 79.2% of all patients classified as T1MI (range 44.2-93.0%) and 40.2% of all T2MI patients (range 0-87.5%). A meta-analysis of 6 studies (44,366 in total) on 2-year mortality showed worse outcome among T2MI patients (RR: 1.52, CI 1.07-2.17, P = 0.02; I 2  = 92%). Risk of reinfarction at 1.6 years was higher among T2MI patients (RR: 1.68, CI 1.22-2.31, P = 0.001; I 2  = 9%)., Conclusions: Classification of T1MI and T2MI varies widely among studies. A standardized approach with clear definitions is needed to avoid misclassification and ensure appropriate patient management.

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.

Background:  Soluble P-selectin (sP-selectin), a biomarker of inflammatory pathologies including cardiovascular disease, is known to have pro-atherosclerotic effects such as the ability to increase leukocyte recruitment and modulate thrombotic response. We aimed to assess the impact of sP-selectin on long-term major adverse cardiovascular events (MACE) in patients after coronary stenting for coronary artery disease., Methods:  We analysed 733 patients of a single-centre registry undergoing percutaneous coronary intervention (PCI) between 2003 and 2006. Plasma samples were analysed for sP-selectin antigen concentration with an enzyme-linked immunoassay. The study population was categorized according to sP-selectin quartiles. Endpoint of the study was long-term MACE, a composite of all-cause death, myocardial infarction (MI) and stroke., Results:  Of the total patient cohort, 361 (49.2%) patients were admitted for stable coronary artery disease and 372 (50.8%) for acute coronary syndrome. Median age was 64 years and 70.7% were male. After a mean follow-up period of 9.7 years, MACE occurred in 344 (46.9%) patients. The primary endpoint components of all-cause death occurred in 211 (28.8%), MI in 88 (12.0%) and ischaemic stroke in 45 (6.1%) patients. After adjustment for confounders, patients in the 2nd, 3rd and 4th quartile were at higher risk for MACE compared with the 1st quartile (hazard ration [HR], 1.234 [0.899-1.695], p  = 0.193; HR, 1.480 [1.085-2.019], p  = 0.013; and HR, 1.571 [1.115-2.152], p  = 0.004). sP-selectin as continuous variable model was significantly associated with MACE after adjustment (HR per 1 ng/mL increase of 1.009 [95% confidence interval, 1.002-1.017]; p  = 0.016)., Conclusion:  Elevated levels of sP-selectin were associated with increased risk for long-term MACE in patients undergoing PCI., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Patients with familial hypercholesterolemia (FH) are at increased risk for premature and subsequent cardiovascular disease. Data on long-term major adverse cardiovascular events (MACE) in patients with FH after percutaneous coronary intervention (PCI) in the era of high-intensity statins are scarce., Objective: We assessed the prognostic impact of clinically diagnosed FH on long-term MACE, a composite of all-cause death, myocardial infarction, and ischemic stroke in patients admitted for stable coronary artery disease (SCAD) or acute coronary syndromes (ACSs) undergoing PCI., Methods: FH was diagnosed according to the Dutch Lipid Clinic Network diagnosis criteria: "Unlikely FH" diagnosis was defined as 0 to 2 points, "possible FH" as 3 to 5 points, and "probable/definite FH" diagnosis as 6 or higher., Results: From a total of 1550 eligible patients (47.4% were admitted for SCAD and 52.6% for ACS), 77 (5.0%) were classified as probable/definite FH, 332 (21.4%) as possible FH, and 1141 (73.6%) as unlikely FH. Mean follow-up was 6.0 ± 2.4 years. After adjustment for possible confounders, patients classified with probable or definite FH (hazard ratio [HR] 1.922 [95% confidence interval (CI) 1.220-2.999]; P = .004), but not patients with possible FH (HR 1.105 [95% CI 0.843-1.447]; P = .470) faced a significant, approximately 2-fold increased risk of MACE compared with patients with unlikely FH., Conclusion: After adjustment for confounders, patients with probable or definite FH faced an approximate 2-fold increased risk for long-term MACE compared with patients without FH despite the widespread use of high-intensity statins. The new option of proprotein convertase subtilisin/kexin type 9 gene inhibitors in addition to other current optimal lipid-lowering strategies might help to further improve clinical outcome in patients with probable/definite FH., (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: In Austria only 41% of patients with treated hypertension (HTN) have their blood pressure (BP) controlled. This study investigated a strategy to improve BP control in primary care., Methods: General practitioners (GPs) were randomized to interventional care vs. standard care and included patients with uncontrolled office BP > 140/90 mm Hg. In interventional care, antihypertensive therapy was up-titrated using a single pill combination (olmesartan, amlodipine and/or hydrochlorothiazde) in 4‑week intervals. In standard care, physicians were encouraged to treat according to the 2013 European Society of Cardiology guidelines for the management of arterial hypertension. The primary endpoint was the proportion of patients with controlled office BP < 140/90 mm Hg at 6 months. The main secondary endpoint was the improvement in 24 h ambulatory BP (ABPM, Clinicaltrials.gov NCT02377661)., Results: Between 2015-2017, 20 GPs contributed to patient recruitment. The trial was discontinued due to slow recruitment after inclusion of 139 eligible patients, 54 of whom were included in the interventional group. A significantly larger proportion of patients in interventional vs. standard care achieved the office BP target (67% ± 26% vs. 39% ± 29%, respectively, mean difference -27.9%, 95% confidence interval CI -54.0%; -1.7%, p = 0.038). The proportion of patients with controlled 24 h ABPM (<130/80 mm Hg) was similar between groups (49% ± 33% vs. 40% ± 34%, respectively, mean difference -8.8%, 95% CI -40.7%; 23.1%, p = 0.57). At baseline, pretreated patients received an average of 1.5 ± 0.8 vs. 1.7 ± 0.9 antihypertensive prescriptions. At 6 months, the respective BP reductions were achieved with 1.2 ± 0.5 prescriptions in interventional vs. 2.0 ± 1.0 in standard care (p < 0.01)., Conclusion: In both groups statistically and clinically significant BP reductions were observed after 6 months. In the interventional care group, a larger proportion of patients achieved the office BP target compared to standard care. The 24 h ambulatory blood pressure levels were controlled in 44% of patients at 6 months, without significant differences between groups. The respective BP reductions were achieved with a significantly lower medication burden in interventional care.

Background and Aims: YKL-40 is an inflammatory marker secreted by macrophages and is expressed in atherosclerotic plaques. YKL-40 increases in coronary artery disease (CAD) with poor coronary collateral vessel development. Higher levels are linked to reduced survival in CAD patients. Studies evaluating YKL-40 in patients with peripheral arterial disease (PAD) are scarce. This study aims to elucidate a possible link between YKL-40 and PAD severity as well as cardiovascular long-term mortality., Methods: YKL-40 was measured at baseline in 365 elderly PAD patients (age 69 ± 10.4, 33.7% women, Fontaine stage I-II) by bead-based multiplex assay. Patients were followed for seven years to assess long-term cardiovascular and all-cause survival by Kaplan-Meier and Cox regression., Results: YKL-40 levels were associated with declining ankle-brachial index (ABI) in PAD patients without Moenckeberg's mediasclerosis (R = -0.189, p=0.002). PAD patients with mediasclerosis exhibited higher YKL-40 levels (p=0.002). Baseline YKL-40 levels were significantly associated with cardiovascular mortality (HR 1.52 (1.21-1.91), p < 0.001) and all-cause mortality (HR 1.45 (1.20-1.75), p < 0.001) over a seven-year observation period. After multivariable adjustment for gender, patient age, known carotid artery disease, known coronary artery disease, smoking status, systolic blood pressure, HbA 1c , low density lipoprotein cholesterol, estimated glomerular filtration rate, aspartate aminotransferase, and C-reactive protein, YKL-40 remained significantly associated with cardiovascular (HR 1.34 (1.02-1.75), p=0.033) and all-cause mortality (HR 1.25 (1.01-1.55), p=0.039)., Conclusions: Increased YKL-40 levels are independently associated with poor long-term cardiovascular survival in peripheral arterial disease patients. Furthermore, YKL-40 correlates with patients' ABI in PAD in the absence of mediasclerosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: Evidence links uric acid (UA) with the promotion of cardiovascular disease. We assessed the prognostic value of UA on long-term major adverse outcomes (MACE) in patients with acute coronary syndrome (ACS), undergoing percutaneous coronary intervention (PCI)., Methods: As primary endpoint, we assessed the association of UA (continuous and dichotomized) with MACE, including cardiovascular death, myocardial infarction (MI) and stroke, using Cox regression and propensity matching. As secondary endpoints, the influence of hyperuricemia (defined as UA levels > 6.0 mg/dl in women, and >7.0 mg/dl in men) was analysed separately for cardiovascular death, MI, and stroke. The incremental prognostic value of UA was tested using the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI)., Results: We included 1215 patients. Hyperuricemia was present in 356 (29.3%) patients. Mean follow-up was 5.5 years. UA (HR 1.091 [1.035-1.150]; p = 0.001) and hyperuricemia (HR 1.750 [1.388-2.207]; p < 0.001) were significantly associated with MACE. Results were consistent between Cox regression and propensity matched analysis. Patients with hyperuricemia had a 1.6-fold increased relative risk for cardiovascular death (p = 0.005) and a 1.5-fold increased risk for MI (p = 0.032). For stroke, hyperuricemia only constituted a confounder (HR 1.104; p = 0.970). The prognostic accuracy of an established risk prediction model was significantly increased by adding UA (continuous NRI p = 0.004; categorical NRI p = 0.029; IDI p = 0.002)., Conclusions: Our data suggest an independent association of elevated UA with long-term MACE in ACS patients undergoing PCI. Whether lowering UA might be beneficial remains to be elucidated in large clinical trials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: We investigated the association between epicardial adipose tissue (EAT) thickness and cardiovascular outcomes in a cohort of high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention., Methods: Of 1198 patients undergoing percutaneous coronary intervention, transthoracic echocardiography was performed in 438 patients during the index hospitalization. EAT thickness was measured in the parasternal long-axis view perpendicularly on the free wall of the right ventricle at end-systole in three consecutive cardiac cycles and then averaged. As the primary outcome measure, a composite of major adverse cardiovascular events - including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke - was investigated after three years of follow-up., Results: Patients were included between 2004 and 2012 and 293 (66.9%) were men. The median EAT thickness was 2.65 mm (interquartile range 2.00-3.00). EAT was correlated with body mass index ( R=0.404; p<0.001), weight ( R=0.314; p<0.001), baseline creatinine ( R=0.118; p=0.014) and baseline glucose ( R=0.129; p=0.007). After a follow-up period of three years, a major adverse cardiovascular event occurred in 64 patients (14.6%) corresponding to 36 (8.2%) with cardiovascular death, 21 (4.8%) with myocardial infarction and seven (1.6%) with stroke. Regarding the primary endpoint, EAT thickness revealed a significant predictive effect on univariate Cox regression (hazards ratio 1.479, 95% CI 1.192-1.953; p=0.006) and multivariate Cox regression analysis (hazards ratio 1.524, 95% CI 1.011-2.267; p=0.038) after adjusting for established cardiovascular confounders., Conclusions: In a cohort of high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention, EAT was associated with established markers of cardiovascular death and had a predictive value for the three-year cardiovascular outcome.

Background: Several studies have shown contradictive findings regarding mortality and hospital admission time in patients presenting with ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the impact of "on-" or "off-hour" admission on short- and long-term all-cause mortality of patients in the advanced Vienna STEMI network between 2003 and 2009., Methods and Results: In total, 2829 patients were included into this analysis. Patients were stratified according to admission time into "on-hour" admission (07:30 until 15:00h on weekdays) and "off-hour" admission (15:00-7:30h on weekdays and 24h on weekends). As endpoint of interest, all-cause mortality was investigated after 30days and 3years of follow-up, the latter for all patients and as Landmark analysis for survivors of the index event. Mean age was 60.5±13.3years, 2048 (72.4%) patients were male and 1260 (44.5%) patients presented with anterior wall infarction. 683 (24.1%) patients were admitted "on-hours", 2146 (75.9%) patients were admitted "off-hours". All-cause death occurred in 176 (6.2%) patients after a follow-up of 30days and in 337 (11.9%) patients after 3years. For short- and long-term all-cause mortality no significant differences could be detected between "on-" and "off-hour" admission in univariate and multivariate Cox proportional hazard analyses as well as for propensity score adjusted outcome analysis., Conclusion: In the Vienna STEMI network, "on-" or "off-hour" admission had no impact on short- and long-term mortality for all-comers presenting with acute STEMI. Our findings confirm the imperative need for well-structured STEMI networks of care, as previous data repeatedly demonstrated increased adverse cardiovascular outcome for "off-hour" admission., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: To this day, there is no data concerning guideline adherence on P2Y12-inhibitors in Austria. Prasugrel and ticagrelor have been shown to be superior to clopidogrel in the treatment of acute coronary syndromes (ACS). However, recent data from European registries showed a reluctant prescription policy with rates of clopidogrel at discharge ranging from 35 to 55%., Methods: In this prospective, multi-centre registry we assessed prescription rates of P2Y12-inhibitors in patients with ACS in four Austrian PCI centres. Parameters associated with the use of clopidogrel have been evaluated in multivariate logistic regression., Results: Between January and June 2015, 808 patients with ACS undergoing PCI were considered for further analysis. 416 (51.5%) presented with STEMI and 392 (48.5%) with NSTE-ACS. Mean age was 65.7 ± 12.4 and 240 (30.9%) were female. Twenty-eight (3.5%) died during the hospital stay. At discharge, 212 (27.2% of all patients) received clopidogrel, 260 (32.2%) prasugrel and 297 (36.8%) ticagrelor, while 11 (1.4%) did not receive any P2Y12-inhibitor. Of those patients, who were discharged with clopidogrel, 117 (55.2%) had no absolute contraindication against a more potent P2Y12-inhibitor. Diagnosis of NSTE-ACS (p<0.001), COPD (p = 0.049), and age (p<0.001) next to factors contributing to absolute contraindication were positively associated with the use of clopidogrel., Conclusions: Despite a high level of care, a considerable number of patients were not treated with the more potent P2Y12-inhibitors. Parameters associated with a presumably higher risk of bleeding and side-effects against the more effective P2Y12 inhibitors were the most prominent factors for the prescription of clopidogrel.

Background: Early identification and treatment of cardiovascular risk factors (CVRFs) is essential to prevent excess morbidity, mortality and healthcare-related costs. We sought to investigate whether an active screening programme at pharmacies could identify a significant proportion of patients with previously undetected CVRFs., Methods and Results: Between April and July 2013, 184 pharmacies in Lower Austria enrolled a total of 6800 participants, in whom body mass index (BMI), blood pressure (BP), total cholesterol and blood glucose were measured. Mean age was 58±17 years and 67.8% were women. 21% of men and 16% of women had a BMI≥30 kg/m 2 . The crude prevalence of diabetes mellitus (DM) was 7%, hypercholesterolaemia was identified in 57%, and 44% had elevated BP. Among fasting individuals (n=1814), DM was found in 18%. In total, 30% were confronted with a CVRF they were previously unaware of, and pharmacists recommended 45% of all participants to actively consult a physician. A first-time diagnosis of a CVRF was most frequent in the age groups between 25 and 64 (32% of participants)., Conclusions: This pharmacy-based approach for cardiovascular risk screening found similar overall prevalences of CVRFs as reported by national surveys, but revealed underdiagnoses, particularly in lower age groups. A previously unknown CVRF was identified in every third individual, frequently prompting the pharmacists to recommend the consultation of a physician. An active screening approach at pharmacies might therefore serve as an effective alternative to the public preventive medical examination, particularly in younger age groups.