| 1. |
- Abdelsayed, Mena, et al.
(författare)
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Repurposing drugs to treat cardiovascular disease in the era of precision medicine
- 2022
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Ingår i: Nature Reviews Cardiology. - : Springer Science and Business Media LLC. - 1759-5002 .- 1759-5010. ; 19:11, s. 751-764
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Forskningsöversikt (refereegranskat)abstract
- Drug repurposing is the use of a given therapeutic agent for indications other than that for which it was originally designed or intended. The concept is appealing because of potentially lower development costs and shorter timelines than are needed to produce a new drug. To date, drug repurposing for cardiovascular indications has been opportunistic and driven by knowledge of disease mechanisms or serendipitous observation rather than by systematic endeavours to match an existing drug to a new indication. Innovations in two areas of personalized medicine — computational approaches to associate drug effects with disease signatures and predictive model systems to screen drugs for disease-modifying activities — support efforts that together create an efficient pipeline to systematically repurpose drugs to treat cardiovascular disease. Furthermore, new experimental strategies that guide the medicinal chemistry re-engineering of drugs could improve repurposing efforts by tailoring a medicine to its new indication. In this Review, we summarize the historical approach to repurposing and discuss the technological advances that have created a new landscape of opportunities.
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| 2. |
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| 3. |
- Back, M, et al.
(författare)
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Anti-inflammatory therapies for atherosclerosis
- 2015
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Ingår i: Nature reviews. Cardiology. - : Springer Science and Business Media LLC. - 1759-5010 .- 1759-5002. ; 12:4, s. 199-211
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Tidskriftsartikel (refereegranskat)
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| 4. |
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| 5. |
- Beamish, Andrew J., et al.
(författare)
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Cardiovascular effects of bariatric surgery
- 2016
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Ingår i: Nature Reviews Cardiology. - : Springer Science and Business Media LLC. - 1759-5002 .- 1759-5010. ; 13:12, s. 730-743
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a major global health problem, and its multisystem effects are inextricably linked with elevated cardiovascular risk and adverse outcomes. The cardiovascular benefits of reversing obesity in adults are well-established. Compared with other weight-loss strategies, programmes that incorporate bariatric surgery for weight loss are beneficial for sustained BMI reduction. A marked improvement in cardiovascular risk factors, including hypertension, dyslipidaemia, inflammation, and type 2 diabetes mellitus, has been observed after bariatric surgery. This broad improvement in cardiovascular risk profile has led to substantial reductions in the risk of myocardial infarction, stroke, and death. As with all procedures, the benefits of bariatric surgery must be weighed against its potential risks. Modern bariatric surgery has an excellent safety profile, but important limitations remain, including the potential for surgical complications and nutritional deficiencies, and the lifelong requirement for nutritional supplementation. Surgery should be considered in patients with severe obesity, especially those with cardiovascular comorbidities. In this Review, we summarize the current management options for patients with obesity, and discuss the effects of bariatric surgery on cardiovascular risk factors and outcomes.
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| 6. |
- Borén, Jan, 1963, et al.
(författare)
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Metabolism of triglyceride-rich lipoproteins in health and dyslipidaemia
- 2022
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Ingår i: Nature Reviews Cardiology. - : Springer Science and Business Media LLC. - 1759-5002 .- 1759-5010. ; 19
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Forskningsöversikt (refereegranskat)abstract
- Accumulating evidence points to the causal role of triglyceride-rich lipoproteins and their cholesterol-enriched remnants in atherogenesis. Genetic studies in particular have not only revealed a relationship between plasma triglyceride levels and the risk of atherosclerotic cardiovascular disease, but have also identified key proteins responsible for the regulation of triglyceride transport. Kinetic studies in humans using stable isotope tracers have been especially useful in delineating the function of these proteins and revealing the hitherto unappreciated complexity of triglyceride-rich lipoprotein metabolism. Given that triglyceride is an essential energy source for mammals, triglyceride transport is regulated by numerous mechanisms that balance availability with the energy demands of the body. Ongoing investigations are focused on determining the consequences of dysregulation as a result of either dietary imprudence or genetic variation that increases the risk of atherosclerosis and pancreatitis. The identification of molecular control mechanisms involved in triglyceride metabolism has laid the groundwork for a 'precision-medicine' approach to therapy. Novel pharmacological agents under development have specific molecular targets within a regulatory framework, and their deployment heralds a new era in lipid-lowering-mediated prevention of disease. In this Review, we outline what is known about the dysregulation of triglyceride transport in human hypertriglyceridaemia.
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| 7. |
- Caliskan, Etem, et al.
(författare)
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Saphenous vein grafts in contemporary coronary artery bypass graft surgery
- 2020
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Ingår i: Nature Reviews Cardiology. - : Nature Publishing Group. - 1759-5002 .- 1759-5010. ; 17:3, s. 155-169
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Forskningsöversikt (refereegranskat)abstract
- Myocardial ischaemia resulting from obstructive coronary artery disease is a major cause of morbidity and mortality in the developed world. Coronary artery bypass graft (CABG) surgery is the gold-standard treatment in many patients with complex multivessel coronary artery disease or left main disease. Despite substantial improvements in the outcome of patients undergoing CABG surgery in the past decade, graft patency remains the 'Achilles' heel' of this procedure. Whereas the use of the left internal mammary artery as a conduit is associated with the highest 10-year patency rate (>90%), saphenous vein grafts - the most commonly used conduit in CABG surgery - fail in 40-50% of treated patients by 10 years after surgery. Vein graft disease (VGD) and failure result from complex pathophysiological processes that can lead to complete occlusion of the graft, affecting long-term clinical outcomes. Optimal harvesting techniques, intraoperative preservation strategies and intraoperative patency control have important roles in the prevention of VGD. In addition, several studies published in the past decade have reported similar mid-term patency rates between vein grafts and arterial grafts when veins are used as a composite graft based on the internal mammary artery. In this Review, we present the latest evidence on the utilization of saphenous vein grafts for CABG surgery and provide an overview of the current practices for the prevention of VGD and vein graft failure.
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| 8. |
- Capodanno, Davide, et al.
(författare)
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Bleeding avoidance strategies in percutaneous coronary intervention
- 2022
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Ingår i: Nature Reviews Cardiology. - : Springer Nature. - 1759-5002 .- 1759-5010. ; 19:2, s. 117-132
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Tidskriftsartikel (refereegranskat)abstract
- For many years, bleeding has been perceived as an unavoidable consequence of strategies aimed at reducing thrombotic complications in patients undergoing percutaneous coronary intervention (PCI). However, the paradigm has now shifted towards bleeding being recognized as a prognostically unfavourable event to the same extent as having a new or recurrent ischaemic or thrombotic complication. As such, in parallel with progress in device and drug development for PCI, there is clinical interest in developing strategies that maximize not only the efficacy but also the safety (for example, by minimizing bleeding) of any antithrombotic treatment or procedural aspect before, during or after PCI. In this Review, we discuss contemporary data and aspects of bleeding avoidance strategies in PCI, including risk stratification, timing of revascularization, pretreatment with antiplatelet agents, selection of vascular access, choice of coronary stents and antithrombotic treatment regimens.
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| 9. |
- Capodanno, Davide, et al.
(författare)
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Dual-pathway inhibition for secondary and tertiary antithrombotic prevention in cardiovascular disease
- 2020
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Ingår i: Nature Reviews Cardiology. - : Springer Science and Business Media LLC. - 1759-5002 .- 1759-5010. ; 17:4, s. 242-257
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Forskningsöversikt (refereegranskat)abstract
- Advances in antiplatelet therapies for patients with cardiovascular disease have improved patient outcomes over time, but the challenge of balancing the risks of ischaemia and bleeding remains substantial. Moreover, many patients with cardiovascular disease have a residual risk of ischaemic events despite receiving antiplatelet therapy. Therefore, novel strategies are needed to prevent clinical events through mechanisms beyond platelet inhibition and with an acceptable associated risk of bleeding. The advent of non-vitamin K antagonist oral anticoagulants, which attenuate fibrin formation by selective inhibition of factor Xa or thrombin, has renewed the interest in dual-pathway inhibition strategies that combine an antiplatelet agent with an anticoagulant drug. In this Review, we highlight the emerging pharmacological rationale and clinical development of dual-pathway inhibition strategies for the prevention of atherothrombotic events in patients with different manifestations of cardiovascular disease, such as coronary artery disease, cerebrovascular disease and peripheral artery disease. Many patients with cardiovascular disease have a residual risk of ischaemic events despite receiving antiplatelet therapy. In this Review, Angiolillo and colleagues discuss the pharmacological rationale and clinical development of dual-pathway inhibition strategies for the prevention of atherothrombotic events in patients with cardiovascular disease.
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| 10. |
- Chakaroun, Rima, 1983, et al.
(författare)
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The potential of tailoring the gut microbiome to prevent and treat cardiometabolic disease
- 2023
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Ingår i: Nature Reviews Cardiology. - : Springer Science and Business Media LLC. - 1759-5002 .- 1759-5010. ; 20:4, s. 217-235
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Tidskriftsartikel (refereegranskat)abstract
- In this Review, Backhed and colleagues summarize the evidence for gut microbiome alterations in cardiometabolic and cardiovascular diseases and the rationale and potential benefit motivating translational approaches to target the gut microbiota and its metabolites for prevention and treatment. Despite milestones in preventive measures and treatment, cardiovascular disease (CVD) remains associated with a high burden of morbidity and mortality. The protracted nature of the development and progression of CVD motivates the identification of early and complementary targets that might explain and alleviate any residual risk in treated patients. The gut microbiota has emerged as a sentinel between our inner milieu and outer environment and relays a modified risk associated with these factors to the host. Accordingly, numerous mechanistic studies in animal models support a causal role of the gut microbiome in CVD via specific microbial or shared microbiota-host metabolites and have identified converging mammalian targets for these signals. Similarly, large-scale cohort studies have repeatedly reported perturbations of the gut microbial community in CVD, supporting the translational potential of targeting this ecological niche, but the move from bench to bedside has not been smooth. In this Review, we provide an overview of the current evidence on the interconnectedness of the gut microbiome and CVD against the noisy backdrop of highly prevalent confounders in advanced CVD, such as increased metabolic burden and polypharmacy. We further aim to conceptualize the molecular mechanisms at the centre of these associations and identify actionable gut microbiome-based targets, while contextualizing the current knowledge within the clinical scenario and emphasizing the limitations of the field that need to be overcome.
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