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Goliasch G.,Medical University of Vienna | Wiesbauer F.,Medical University of Vienna | Blessberger H.,Medical University of Vienna | Blessberger H.,Johannes Kepler University | And 9 more authors.
Journal of Clinical Lipidology | Year: 2015

Background Remnant cholesterol has been defined as the cholesterol present in triglyceride-rich remnant lipoproteins. Elevated levels of remnant cholesterol have been associated with increased cardiovascular risk. Acute myocardial infarction (AMI) in very young individuals (≤40 years) represents a rare disease with a typical risk factor profile and a lipid phenotype that is characterized by a predominance of elevated triglyceride-rich lipoproteins. Objective The aim of this study was to investigate the role of remnant cholesterol in premature AMI. Methods We prospectively enrolled 302 patients into our multicenter case-control study comprising 102 consecutive myocardial infarction survivors (≤40 years) and 200 hospital controls. Myocardial infarction patients were frequency matched for age, gender, and center. Remnant cholesterol was calculated from standard lipid parameters. Results Remnant cholesterol was 1.7-fold higher in premature AMI patients compared with controls (61.1 ± 36.8 vs 35.8 ± 16.8 mg/dL; P < .001). Remnant cholesterol was the lipid fraction most strongly associated with premature myocardial infarction (odds ratio 3.87; 95% confidence interval 2.26-6.64; P < .001) for an increase of 1-standard deviation. This observation was independent from clinical risk factors and plasma lipid levels. Conclusions Remnant cholesterol is strongly associated with premature myocardial infarction, can be easily calculated, and might serve as a new potent risk marker in this young patient population. © 2015 National Lipid Association. Source

Rubboli A.,Laboratory of Interventional Cardiology | Agewall S.,University of Oslo | Huber K.,Cardiology and Intensive Care Medicine | Lip G.Y.H.,University of Birmingham
International Journal of Cardiology | Year: 2015

The antithrombotic management of patients on oral anticoagulation (OAC), with either warfarin or non-vitamin K-antagonist oral anticoagulants (NOACs), undergoing percutaneous coronary intervention with stent (PCI-S) has been recently addressed in a joint European consensus document. In accordance, triple therapy (TT) of OAC, aspirin and clopidogrel should generally be given as the initial therapy. More uncertainty exists over whether warfarin or a NOAC should be added in patients already on dual antiplatelet therapy of aspirin and clopidogrel (DAPT) after recent PCI-S. Upon review of available data, it appears that the risk of major bleeding of TT as compared to DAPT is similar with either warfarin or a NOAC. In particular, TT consistently appears associated to an approximately 2.5 fold increase in the risk of major bleeding. Because of the higher convenience, NOACs might be considered the preferred OAC to be added to DAPT. Given the reported different safety profiles of the various NOACs on the incidence of major, and gastrointestinal, bleeding, the NOACs, and the dose, showing the greatest safety in this regard should be selected. In accordance, dabigatran 110 mg and apixaban 2.5 mg twice daily appear as the most valuable options in patients who are not and who are respectively, at increased risk of bleeding. As an alternative, apixaban 5 mg twice daily might be considered in patients at risk of bleeding not increased, whereas rivaroxaban 15 mg once daily may be considered in the presence of increased risk of bleeding (essentially when related to moderate renal impairment). © 2015 Elsevier Ireland Ltd. Source

Vranckx P.,Hartcentrum Hasselt | White H.D.,Green City | Huang Z.,Pratt Institute | Mahaffey K.W.,Stanford University | And 13 more authors.
Journal of the American College of Cardiology | Year: 2016

Background The Bleeding Academic Research Consortium (BARC) scale has been proposed to standardize bleeding endpoint definitions and reporting in cardiovascular trials. Validation in large cohorts of patients is needed. Objectives This study sought to investigate the relationship between BARC-classified bleeding and mortality and compared its prognostic value against 2 validated bleeding scales: TIMI (Thrombolysis In Myocardial Infarction) and GUSTO (Global Use of Strategies to Open Occluded Arteries). Methods We analyzed bleeding in 12,944 patients with acute coronary syndromes without ST-segment elevation, with or without early invasive strategy. The main outcome measure was all-cause death. Results During follow-up (median: 502 days), noncoronary artery bypass graft (CABG) bleeding occurred in 1,998 (15.4%) patients according to BARC (grades 2, 3, or 5), 484 (3.7%) patients according to TIMI minor/major, and 514 (4.0%) patients according to GUSTO moderate/severe criteria. CABG-related bleeding (BARC 4) occurred in 155 (1.2%) patients. Patients with BARC (2, 3, or 4) bleeding had a significant increase in risk of death versus patients without bleeding (BARC 0 or 1); the hazard was highest in the 30 days after bleeding (hazard ratio: 7.35; 95% confidence interval: 5.59 to 9.68; p < 0.0001) and remained significant up to 1 year. The hazard of mortality increased progressively with non-CABG BARC grades. BARC 4 bleeds were significantly associated with mortality within 30 days (hazard ratio: 10.05; 95% confidence interval: 5.41 to 18.69; p < 0.0001), but not thereafter. Inclusion of BARC (2, 3, or 4) bleeding in the 1-year mortality model with baseline characteristics improved it to an extent comparable to TIMI minor/major and GUSTO moderate/severe bleeding. Conclusions In patients with acute coronary syndromes without ST-segment elevation, bleeding assessed with the BARC scale was significantly associated with risk of subsequent death up to 1 year after the event and risk of mortality increased gradually with higher BARC grades. Our results support adoption of the BARC bleeding scale in ACS clinical trials. © 2016 American College of Cardiology Foundation. Source

Schror K.,Universitatsklinikum Dusseldorf | Huber K.,Cardiology and Intensive Care Medicine
Thrombosis and Haemostasis | Year: 2015

Taken together, current evidence suggests that conventional antiplatelet drugs, such as aspirin, clopidogrel, prasugrel and ticagrelor also have antiinflammatory actions in different experimental settings and clinical conditions. These actions are thought to be primarily related to their antiplatelet effect. While there is significant evidence for aspirin-related antiinflammatory antiplatelet actions, the situation with ADP-antagonists is less clear, as it has been reported (28) that treatment with ticagrelor and clopidogrel did not lead to significant differences regarding the inflammatory biomarkers CRP, IL-6, and sCD40L in patients with NSTE-ACS among treatment groups at baseline, discharge, and at four weeks (23). However, these actions will be seen during DAPT and likely the anti - aggregatory effect might also be stronger with combined use. © Schattauer 2015. Source

Kozarov E.,Columbia University | Huber K.,Cardiology and Intensive Care Medicine | Wojta J.,Medical University of Vienna
Current Pharmaceutical Design | Year: 2015

Atherosclerosis is a systemic inflammatory disease leading to lipid-laden inflammatory lesions in the arterial walls that may destabilize and rupture. It is becoming clear that addressing the “classical” risk factors for atherosclerosis does not entirely reduce the risk of cardiovascular events. Novel biomarkers to be used in highthroughput assays are necessary for diagnosis, for determination of the residual risk and for monitoring the effects of the therapy. Since inflammation is a hallmark of atherosclerosis, tests for pro-inflammatory biomarkers have been introduced such as for hsCRP, fibrinogen and IL-6, with many more at different stages of development. There has been a dearth of novel approaches for the diagnosis and management of atherosclerosis, reflected in a continuous reliance on LDL cholesterol as a proven target of investigations. To bring another perspective, here we briefly overview the accumulated epidemiological and sero-epidemiological evidence suggesting systemic infections as a component of atherosclerotic inflammations. We have shown that different individuals’ plaques are colonized with different bacterial species (atherosclerosis microbiota). Most of the time the pathogens are likely in an intracellular state, shielded from the host immune responses. There are controlled clinical trials and metaanalyses that corroborate the infections, specifically periodontal disease as a contributing risk factor of atherosclerosis. Infection-related markers, including transcriptome signatures, may identify latent infection patients with sub-clinical disease. Thus, the emerging infection- associated markers of inflammation could complement the existing ones and their use as companion diagnostics for atherosclerosis should stimulate the growing field of personalized medicine within cardiovascular diseases. © 2015 Bentham Science Publishers. Source

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