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  • Ferguson, Lynnette R., et al. (author)
  • Guide and Position of the International Society of Nutrigenetics/Nutrigenomics on Personalised Nutrition : Part 1 - Fields of Precision Nutrition
  • 2016
  • In: Journal of Nutrigenetics and Nutrigenomics. - : S. Karger AG. - 1661-6499. ; 9:1, s. 12-27
  • Journal article (peer-reviewed)abstract
    • Diversity in the genetic profile between individuals and specific ethnic groups affects nutrient requirements, metabolism and response to nutritional and dietary interventions. Indeed, individuals respond differently to lifestyle interventions (diet, physical activity, smoking, etc.). The sequencing of the human genome and subsequent increased knowledge regarding human genetic variation is contributing to the emergence of personalized nutrition. These advances in genetic science are raising numerous questions regarding the mode that precision nutrition can contribute solutions to emerging problems in public health, by reducing the risk and prevalence of nutrition-related diseases. Current views on personalized nutrition encompass omics technologies (nutrigenomics, transcriptomics, epigenomics, foodomics, metabolomics, metagenomics, etc.), functional food development and challenges related to legal and ethical aspects, application in clinical practice, and population scope, in terms of guidelines and epidemiological factors. In this context, precision nutrition can be considered as occurring at three levels: (1) conventional nutrition based on general guidelines for population groups by age, gender and social determinants; (2) individualized nutrition that adds phenotypic information about the person's current nutritional status (e.g. anthropometry, biochemical and metabolic analysis, physical activity, among others), and (3) genotype-directed nutrition based on rare or common gene variation. Research and appropriate translation into medical practice and dietary recommendations must be based on a solid foundation of knowledge derived from studies on nutrigenetics and nutrigenomics. A scientific society, such as the International Society of Nutrigenetics/Nutrigenomics (ISNN), internationally devoted to the study of nutrigenetics/nutrigenomics, can indeed serve the commendable roles of (1) promoting science and favoring scientific communication and (2) permanently working as a 'clearing house' to prevent disqualifying logical jumps, correct or stop unwarranted claims, and prevent the creation of unwarranted expectations in patients and in the general public. In this statement, we are focusing on the scientific aspects of disciplines covering nutrigenetics and nutrigenomics issues. Genetic screening and the ethical, legal, social and economic aspects will be dealt with in subsequent statements of the Society.
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  • Gargani, Luna, et al. (author)
  • Detecting the vulnerable carotid plaque : The Carotid Artery Multimodality imaging Prognostic study design
  • 2022
  • In: Journal of Cardiovascular Medicine. - 1558-2027. ; 23:7, s. 466-473
  • Journal article (peer-reviewed)abstract
    • BackgroundCarotid artery disease is highly prevalent and a main cause of ischemic stroke and vascular dementia. There is a paucity of information on predictors of serious vascular events. Besides percentage diameter stenosis, international guidelines also recommend the evaluation of qualitative characteristics of carotid artery disease as a guide to treatment, but with no agreement on which qualitative features to assess. This inadequate knowledge leads to a poor ability to identify patients at risk, dispersion of medical resources, and unproven use of expensive and resource-consuming techniques, such as magnetic resonance imaging, positron emission tomography, and computed tomography.ObjectivesThe Carotid Artery Multimodality imaging Prognostic (CAMP) study will: prospectively determine the best predictors of silent and overt ischemic stroke and vascular dementia in patients with asymptomatic subcritical carotid artery disease by identifying the noninvasive diagnostic features of the 'vulnerable carotid plaque'; assess whether 'smart' use of low-cost diagnostic methods such as ultrasound-based evaluations may yield at least the same level of prospective information as more expensive techniques.Study designWe will compare the prognostic/predictive value of all proposed techniques with regard to silent or clinically manifest ischemic stroke and vascular dementia. The study will include ≥300 patients with asymptomatic, unilateral, intermediate degree (40-60% diameter) common or internal carotid artery stenosis detected at carotid ultrasound, with a 2-year follow-up. The study design has been registered on Clinicaltrial.gov on December 17, 2020 (ID number NCT04679727).
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  • Graham, Ian, et al. (author)
  • European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
  • 2007
  • In: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - : Oxford University Press (OUP). - 1741-8267. ; 14 Suppl 2
  • Journal article (peer-reviewed)abstract
    • Other experts who contributed to parts of the guidelines: Edmond Walma, Tony Fitzgerald, Marie Therese Cooney, Alexandra Dudina European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson), John Camm, Raffaele De Caterina, Veronica Dean, Kenneth Dickstein, Christian Funck-Brentano, Gerasimos Filippatos, Irene Hellemans, Steen Dalby Kristensen, Keith McGregor, Udo Sechtem, Sigmund Silber, Michal Tendera, Petr Widimsky, Jose Luis Zamorano Document reviewers: Irene Hellemans (CPG Review Co-ordinator), Attila Altiner, Enzo Bonora, Paul N. Durrington, Robert Fagard, Simona Giampaoli, Harry Hemingway, Jan Hakansson, Sverre Erik Kjeldsen, Mogens Lytken Larsen, Giuseppe Mancia, Athanasios J. Manolis, Kristina Orth-Gomer, Terje Pedersen, Mike Rayner, Lars Ryden, Mario Sammut, Neil Schneiderman, Anton F. Stalenhoef, Lale Tokgözoglu, Olov Wiklund, Antonis Zampelas
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  • Lopes, Renato D., et al. (author)
  • Digoxin and Mortality in Patients With Atrial Fibrillation
  • 2018
  • In: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 71:10, s. 1063-1074
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Digoxin is widely used in patients with atrial fibrillation (AF). OBJECTIVES The goal of this paper was to explore whether digoxin use was independently associated with increased mortality in patients with AF and if the association was modified by heart failure and/or serum digoxin concentration.METHODS: The association between digoxin use and mortality was assessed in 17,897 patients by using a propensity score-adjusted analysis and in new digoxin users during the trial versus propensity score-matched control participants. The authors investigated the independent association between serum digoxin concentration and mortality after multivariable adjustment.RESULTS: At baseline, 5,824 (32.5%) patients were receiving digoxin. Baseline digoxin use was not associated with an increased risk of death (adjusted hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 0.96 to 1.23; p = 0.19). However, patients with a serum digoxin concentration $ 1.2 ng/ml had a 56% increased hazard of mortality (adjusted HR: 1.56; 95% CI: 1.20 to 2.04) compared with those not on digoxin. When analyzed as a continuous variable, serum digoxin concentration was associated with a 19% higher adjusted hazard of death for each 0.5-ng/ml increase (p = 0.0010); these results were similar for patients with and without heart failure. Compared with propensity score-matched control participants, the risk of death (adjusted HR: 1.78; 95% CI: 1.37 to 2.31) and sudden death (adjusted HR: 2.14; 95% CI: 1.11 to 4.12) was significantly higher in new digoxin users.CONCLUSIONS: In patients with AF taking digoxin, the risk of death was independently related to serum digoxin concentration and was highest in patients with concentrations $ 1.2 ng/ml. Initiating digoxin was independently associated with higher mortality in patients with AF, regardless of heart failure.
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  • Patrono, Carlo, et al. (author)
  • Antiplatelet agents for the treatment and prevention of atherothrombosis
  • 2011
  • In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 32:23, s. 2922-32
  • Research review (peer-reviewed)abstract
    • The clinical pharmacology of antiplatelet drugs has been reviewed previously by the European Society of Cardiology (ESC) Task force and by the 8th American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines. Moreover, information on the efficacy and safety of antiplatelet drugs in the treatment and prevention of atherothrombosis is provided by collaborative meta-analyses of 287 secondary prevention trials and 6 primary prevention trials. The present document intends to provide practicing physicians with an updated instrument to guide their choice of the most suitable antiplatelet strategy for the individual patient at risk, or with different clinical manifestations, of atherothrombosis.
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  • Sjögren, Per, et al. (author)
  • Markers of endothelial activity are related to components of the metabolic syndrome, but not to circulating concentrations of the advanced glycation end-product N epsilon-carboxymethyl-lysine in healthy Swedish men
  • 2007
  • In: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 195:2, s. e168-e175
  • Journal article (peer-reviewed)abstract
    • Endothelial function is considered important in the development of cardiovascular diseases and type 2 diabetes. Circulating advanced glycation end-products (AGEs) and dietary components have been shown to affect endothelial function in type 2 diabetics, but determinants of endothelial function in a non-diabetic population are more poorly investigated. Therefore, we investigated relationships between dietary habits, AGEs and endothelial activation in men with isolated metabolic disturbances. Circulating markers of endothelial activation (soluble forms of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and von Willebrand factor) and plasma N epsilon-carboxymethyl-lysine (CML, the predominant AGE in human plasma) were analyzed in a cross-sectional study of 294 healthy men. Individuals completed a 7-day dietary record, and metabolic and inflammatory parameters were determined. NCEP/ATPIII-criteria were used to define the metabolic syndrome. Endothelial activation was higher in individuals with the metabolic syndrome, and was positively related to certain features of the syndrome (insulin, glucose, inflammation and obesity), but not to others (triacylglycerol and blood pressure). Dietary factors were related to endothelial activation, but CML was not. Multivariate analysis revealed energy and alcohol intake, along with insulin and markers of oxidative stress and inflammation, to be positive predictors of endothelial activation. In this cohort of otherwise healthy men, endothelial activation was increased in individuals with the full metabolic syndrome, but not in those with only some of the components of the metabolic syndrome. Insulin resistance, inflammation, oxidative stress, the dietary intake of energy and alcohol, but not plasma CML, predicted endothelial activation in these men.
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  • Zimarino, Marco, et al. (author)
  • Left ventricular size predicts clinical benefit after percutaneous mitral valve repair for secondary mitral regurgitation : A systematic review and meta-regression analysis
  • 2020
  • In: Cardiovascular Revascularization Medicine. - : Elsevier BV. - 1553-8389. ; 21:7, s. 857-864
  • Journal article (peer-reviewed)abstract
    • Background: The benefit of percutaneous mitral valve repair (PMVR) in patients with secondary MR is still debated. We aimed to compare the outcome of PMVR with optimal medical therapy (OMT) versus OMT alone in patients with secondary mitral regurgitation (MR) and to assess the role of potential effect modifiers. Methods: We performed a systematic review and meta-analysis of 2 randomized clinical trials (RCT) and 7 non-randomized observational studies (nROS). Hazard ratios (HR) and 95% confidence intervals (CI) were pooled through inverse variance random-effects model to compute the summary effect size for all-cause death, cardiovascular death and cardiac-related hospitalization. Subgroup and meta-regression analysis were also performed. Results: An overall population of 3118 individuals (67% men; mean age, 73 years) was included: 1775 PMVR+OMT and 1343 OMT patients, with mean follow-up of 24 ± 15 months. PMVR+OMT was associated with a lower risk of all-cause death (HR: 0.77; 95% CI: 0.68–0.87), cardiovascular death (HR: 0.55; 95% CI: 0.34–0.89) and cardiac-related hospitalization (HR:0.77; 95% CI: 0.64–0.92). Meta-regression analysis showed that larger left ventricular end-diastolic volume index (LVEDVI) portends higher risk of all-cause death, cardiovascular death and cardiac-related hospitalization after PMVR (p < 0.001 for all). Conclusions: This study-level meta-analysis shows that PMVR+OMT is associated with reduced all-cause death, cardiovascular death and cardiac-related hospitalization when compared with OMT alone in secondary MR. LVEDVI is a predictive marker of efficacy, as patients with smaller LVEDVI have been shown to derive the largest benefit from PMVR.
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  • Alexander, John H., et al. (author)
  • Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome
  • 2011
  • In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 365:8, s. 699-708
  • Journal article (peer-reviewed)abstract
    • Background: Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome.Methods: We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events.Results: The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P = 0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P = 0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo.Conclusions: The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events.
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  • Bisaccia, Giandomenico, et al. (author)
  • Cardiovascular Morbidity and Mortality Related to Non-Alcoholic Fatty Liver Disease : a Systematic Review and Meta-Analysis
  • 2023
  • In: Current Problems in Cardiology. - : Elsevier BV. - 0146-2806 .- 1535-6280. ; 48:6
  • Research review (peer-reviewed)abstract
    • BACKGROUND AND AIMS: Whether non-alcoholic fatty liver disease (NAFLD) is a cardiovascular (CV) risk factor is debated. We performed a systematic review and meta-analysis to assess the CV morbidity and mortality related to NAFLD in the general population, and to determine whether CV risk is comparable between lean and non-lean NAFLD phenotypes.METHODS AND RESULTS: We searched multiple databases, including PubMed, Embase, and the Cochrane Library, for observational studies published through 2022 that reported the risk of CV events and mortality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for all-cause mortality, CV mortality, myocardial infarction (MI), stroke, atrial fibrillation (AF), and major adverse cardiovascular and cerebrovascular events (MACCE) were assessed through random-effect meta-analysis. We identified 33 studies and a total study population of 10,592,851 individuals (mean age 53±8; male sex 50%; NAFLD 2,9%). Mean follow-up was 10±6 years. Pooled ORs for all-cause and CV mortality were respectively 1.14 (95%CI 0.78-1.67) and 1.13 (95%CI 0.57-2.23), indicating no significant association between NAFLD and mortality. NAFLD was associated with increased risk of MI (OR 1.6; 95%CI 1.5-1.7), stroke (OR 1.6; 95%CI 1.2-2.1), atrial fibrillation (OR 1.7; 95%CI 1.2-2.3) and MACCE (OR 2.3; 95%CI 1.3-4.2). Compared with non-lean NAFLD, lean NAFLD was associated with increased CV mortality (OR 1.50; 95%CI 1.1-2.0), but similar all-cause mortality and risk of MACCE.CONCLUSIONS: While NAFLD may not be a risk factor for total and CV mortality, it is associated with excess risk of non-fatal CV events. Lean and non-lean NAFLD phenotypes exhibit distinct prognostic profiles and should receive equitable clinical care.
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  • Christersson, Christina, et al. (author)
  • Effect of apixaban compared with warfarin on coagulation markers in atrial fibrillation.
  • 2019
  • In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 105:3, s. 235-242
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: Compare the effect of apixaban and warfarin on coagulation and primary haemostasis biomarkers in atrial fibrillation (AF).METHODS: The biomarker substudy from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF randomised to treatment with apixaban or warfarin. Sixty per cent of patients used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand factor (vWF) antigen were analysed at randomisation and after 2 months of study treatment.RESULTS: In patients not on VKA treatment at randomisation, F1+2 and D-dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by 59% and 38%, respectively, with warfarin (p<0.0001 for treatment differences for both). In patients on VKA at randomisation, F1+2 and D-dimer levels increased by 41% and 10%, respectively, with apixaban and decreased by 37% and 11%, respectively, with warfarin (p<0.0001 for treatment differences for both). sCD40L levels were slightly increased at 2 months, regardless of VKA or randomised treatment. Apixaban and warfarin also both reduced vWF antigen regardless of VKA treatment. The efficacy (stroke) and safety (bleeding) of apixaban compared with warfarin was similar irrespectively of biomarker levels at 2 months.CONCLUSIONS: Treatment with apixaban compared with warfarin for stroke prevention in patients with AF was associated with less reduction in thrombin generation and fibrin turnover. This effect of apixaban could contribute to the clinical results where apixaban was superior to warfarin both in stroke prevention and in reducing bleeding risk.TRIAL REGISTRATION NUMBER: NCT00412984.
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  • Dalgaard, Frederik, et al. (author)
  • Patients With Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial
  • 2020
  • In: Circulation. - 0009-7322 .- 1524-4539. ; 141:1, s. 10-20
  • Journal article (peer-reviewed)abstract
    • Background:The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with oral anticoagulants has been associated with an increased risk of bleeding. We investigated the risk of bleeding and major cardiovascular outcomes in patients with atrial fibrillation taking NSAIDs and apixaban or warfarin.Methods:The ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201) compared apixaban with warfarin in patients with atrial fibrillation at an increased risk of stroke. Patients in ARISTOTLE without severe renal (creatine clearance ≤30 mL/min) or liver disease were included in this analysis (n=17 423). NSAID use at baseline, NSAID use during the trial (incident NSAID use), and never users were described. The primary outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding, gastrointestinal bleeding, heart failure hospitalization, stroke or systemic embolism, and all-cause mortality. NSAID use during the trial, and the interaction between randomized treatment, was analyzed using time-dependent Cox proportional hazards models.Results:Those with baseline NSAID use (n=832 [4.8%]), incident NSAID use (n=2185 [13.2%]), and never users were similar in median age (age [25th, 75th]; 70 [64, 77] versus 70 [63, 75] versus 70 [62, 76]). Those with NSAID use at baseline and incident NSAID use were more likely to have a history of bleeding than never users (24.5% versus 21.0% versus 15.6%, respectively). During a median follow-up (25th, 75th) of 1.8 (1.4, 2.3) years and when excluding those taking NSAID at baseline, we found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR], 1.61 [95% CI, 1.11–2.33]) and clinically relevant nonmajor bleeding (HR, 1.70 [95% CI, 1.16–2.48]), but not gastrointestinal bleeding. No significant interaction was observed between NSAID use and randomized treatment for any outcome.Conclusions:A substantial number of patients in the ARISTOTLE trial took NSAIDs. Incident NSAID use was associated with major and clinically relevant nonmajor bleeding, but not with gastrointestinal bleeding. The safety and efficacy of apixaban versus warfarin appeared not significantly to be altered by NSAID use. This study warrants more investigation of the effect of NSAIDs on the outcomes of patients treated with apixaban.Clinical Trial Registration:URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984.
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  • De Caterina, Raffaele, et al. (author)
  • Comparison of Dabigatran Plus a P2Y12 Inhibitor With Warfarin-Based Triple Therapy Across Body Mass Index in RE-DUAL PCI.
  • 2020
  • In: American Journal of Medicine. - : Elsevier BV. - 0002-9343 .- 1555-7162. ; 133:11, s. 1302-1312
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Body mass index (BMI) affects drug levels of nonvitamin K antagonist oral anticoagulants. We sought to assess whether BMI affected outcomes in the RE-DUAL PCI trial.METHODS: RE-DUAL PCI (NCT02164864) evaluated the safety and efficacy of a dual-antithrombotic-therapy regimen using dabigatran (110 mg or 150 mg twice daily and a P2Y12 platelet antagonist) in comparison with triple therapy of warfarin, aspirin, and a P2Y12 platelet inhibitor in 2725 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI). We compared the risk of first International Society on Thrombosis and Haemostasis (ISTH)-defined major or clinically relevant nonmajor bleeding events (primary endpoint) and the composite of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization (main efficacy endpoint) in relation to baseline BMI.RESULTS: Median (range) BMI was 28.1 (14-66) kg/m2. Dabigatran dual therapy versus warfarin triple therapy had relevantly and similarly lower rates of bleeding at both 110 mg and 150 mg twice-daily doses, irrespective of BMI. Thromboembolic event rates appeared consistent across categories of BMI, including those <25 and ≥35 kg/m2 (P for interaction: 0.806 and 0.279, respectively).CONCLUSIONS: The reduction in bleeding with dabigatran dual therapy compared with warfarin triple therapy in patients here evaluated appears consistent across BMI categories.
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