European Heart Journal (2013) 34, 3035–3087 ESC GUIDELINES doi:10.1093/eurheartj/eht108 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD The Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Downloaded from Authors/Task Force Members: Lars Ryde´n* (ESC Chairperson) (Sweden), Peter J. Grant* (EASD Chairperson) (UK), Stefan D. Anker (Germany), Christian Berne (Sweden), Francesco Cosentino (Italy), Nicolas Danchin (France), Christi Deaton (UK), Javier Escaned (Spain), Hans-Peter Hammes (Germany), http://eurheartj.oxfordjournals.org/ Heikki Huikuri (Finland), Michel Marre (France), Nikolaus Marx (Germany), Linda Mellbin (Sweden), Jan Ostergren (Sweden), Carlo Patrono (Italy), Petar Seferovic (Serbia), Miguel Sousa Uva (Portugal), Marja-Riita Taskinen (Finland), Michal Tendera (Poland), Jaakko Tuomilehto (Finland), Paul Valensi (France), Jose Luis Zamorano (Spain) ESC Committee for Practice Guidelines (CPG): Jose Luis Zamorano (Chairperson) (Spain), Stephan Achenbach (Germany), Helmut Baumgartner (Germany), Jeroen J. Bax (Netherlands), He´ctor Bueno (Spain), Veronica Dean by guest on September 19, 2014 (France), Christi Deaton (UK), Çetin Erol (Turkey), Robert Fagard (Belgium), Roberto Ferrari (Italy), David Hasdai (Israel), Arno W. Hoes (Netherlands), Paulus Kirchhof (Germany UK), Juhani Knuuti (Finland), Philippe Kolh (Belgium), Patrizio Lancellotti (Belgium), Ales Linhart (Czech Republic), Petros Nihoyannopoulos (UK), Massimo F. Piepoli (Italy), Piotr Ponikowski (Poland), Per Anton Sirnes (Norway), Juan Luis Tamargo (Spain), Michal Tendera (Poland), Adam Torbicki (Poland), William Wijns (Belgium), Stephan Windecker (Switzerland). Document Reviewers: Guy De Backer (Review Coordinator) (Belgium), Per Anton Sirnes (CPG Review Coordinator) (Norway), Eduardo Alegria Ezquerra (Spain), Angelo Avogaro (Italy), Lina Badimon (Spain), Elena Baranova (Russia), Helmut Baumgartner (Germany), John Betteridge (UK), Antonio Ceriello (Spain), Robert Fagard (Belgium), Christian Funck-Brentano (France), Dietrich C. Gulba (Germany), David Hasdai (Israel), Arno W. Hoes (Netherlands), John K. Kjekshus (Norway), Juhani Knuuti (Finland), Philippe Kolh (Belgium), Eli Lev (Israel), Christian Mueller (Switzerland), Ludwig Neyses (Luxembourg), Peter M. Nilsson (Sweden), Joep Perk (Sweden), Piotr Ponikowski (Poland), Zˇ eljko Reiner (Croatia), Naveed Sattar (UK), Volker Scha¨chinger (Germany), Andre´ Scheen (Belgium), *Corresponding authors: The two chairmen equally contributed to the document. Chairperson ESC: Professor Lars Ryde´n, Cardiology Unit, Department of Medicine Solna, Karolinska Institute, Solna SE-171, 76 Stockholm, Sweden, Tel: +46 8 5177 2171, Fax: +46 8 34 49 64, Email: [email protected]; Chairperson EASD: Professor Peter J. Grant, Division Of Cardio- vascular & Diabetes Research, University Of Leeds, Clarendon Way, Leeds LS2 9JT, United Kingdom. Tel: +44 113 343 7721, Fax: +44 113 343 7738, Email: [email protected] Other ESC entities having participated in the development of this document: Associations: Acute Cardiovascular Care Association (ACCA), European Association of Cardiovascular Imaging (EACVI), European Association for Cardiovascular Prevention & Rehabili- tation (EACPR), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA) Working Groups: Coronary Pathophysiology and Microcirculation, Thrombosis, Cardiovascular Surgery Councils: Cardiovascular Nursing and Allied Professions, Council for Cardiology Practice, Council on Cardiovascular Primary Care, Cardiovascular Imaging The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC. Disclaimer. The ESC Guidelines represent the views of the ESC and EASD and were arrived at after careful consideration of the available evidence at the time they were written. Health professionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient and, where appropriate and necessary, the patient’s guardian or carer. It is also the health professional’s responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription. & The European Society of Cardiology 2013. All rights reserved. For permissions please email: [email protected] 3036 ESC Guidelines Henrik Schirmer (Norway), Anna Stro¨ mberg (Sweden), Svetlana Sudzhaeva (Belarus), Juan Luis Tamargo (Spain), Margus Viigimaa (Estonia), Charalambos Vlachopoulos (Greece), Robert G. Xuereb (Malta). The disclosure forms of the authors and reviewers are available on the ESC website www.escardio.org/guidelines Online publish-ahead-of-print 30 August 2013 ------------------------------------------------------------------------------------------------------------------------------------------------------ Keywords Guidelines † Diabetes mellitus † Cardiovascular disease † Impaired glucose tolerance † Patient management † Prevention † Epidemiology † Prognosis † Diagnostics † Risk factors † Pharmacological treatment † Coronary Interventions Table of Contents Downloaded from 1. Preamble . .3039 6.2 Glucose control . .3053 2. Introduction . .3040 6.2.1. Microvascular disease (retinopathy, nephropathy, 3. Abnormalities of glucose metabolism and cardiovascular disease 3041 neuropathy) . .3053 3.1 Definition, classification and diagnosis . .3041 6.2.2. Macrovascular disease (cerebral, coronary and 3.2 Epidemiology . .3043 peripheral artery disease) . .3053 3.3 Screening for disorders of glucose metabolism . .3043 6.2.3. Medium-term effects of glycaemic control . .3053 http://eurheartj.oxfordjournals.org/ 3.4 Disorders of glucose metabolism and cardiovascular 6.2.4. Long-term effects of glycaemic control . .3053 disease . .3044 6.2.5. Glycaemic targets . .3054 3.5 Delaying conversion to type 2 diabetes mellitus . .3046 6.2.6. Glucose-lowering agents . .3054 3.6 Recommendations for diagnosis of disorders of glucose 6.2.7. Special considerations . .3055 metabolism . .3046 6.2.8. Gaps in knowledge . .3056 4. Molecular basis of cardiovascular disease in diabetes mellitus . .3046 6.2.9. Recommendations for glycaemic control in diabetes 3056 4.1 The cardiovascular continuum in diabetes mellitus . .3046 6.3 Blood pressure . .3056 4.2 Pathophysiology of insulin resistance in type 2 diabetes 6.3.1. Treatment targets . .3056 mellitus . .3047 6.3.2. Managing blood pressure-lowering . .3057 by guest on September 19, 2014 4.3 Endothelial dysfunction, oxidative stress and vascular 6.3.3. Conclusion . .3057 inflammation . .3047 6.3.4. Gaps in knowledge . .3057 4.4 Macrophage dysfunction . .3047 6.3.5. Recommendations for blood pressure control in 4.5 Atherogenic dyslipidaemia . .3048 diabetes . .3058 4.6 Coagulation and platelet function . .3048 6.4 Dyslipidaemia . .3058 4.7 Diabetic cardiomyopathy . .3049 6.4.1. Pathophysiology . .3058 4.8 The metabolic syndrome . .3049 6.4.2. Epidemiology . .3058 4.9 Endothelial progenitor cells and vascular repair . .3049 6.4.3. Management of dyslipidaemia . .3059 4.10 Conclusions . .3049 6.4.4. Gaps in current knowledge . .3060 5. Cardiovascular risk assessment in patients with dysglycaemia . .3049 6.4.5. Recommendations on management of dyslipidaemia 5.1 Risk scores developed for people without diabetes . .3049 in diabetes . .3061 5.2 Evaluation of cardiovascular risk in people with pre- 6.5 Platelet function . .3061 diabetes . .3050 6.5.1. Aspirin . .3061 5.3 Risk engines developed for people with diabetes . .3050 6.5.2. P2Y12 receptor blockers . .3062 5.4 Risk assessment based on biomarkers and imaging . .3050 6.5.3. Gaps in knowledge . .3062 5.5 Gaps in knowledge . .3050 6.5.4. Recommendations for antiplatelet therapy in patients 5.6 Recommendations for cardiovascular risk assessment in with diabetes . .3062 diabetes . .3051 6.6 Multifactorial approaches . .3062 6. Prevention of cardiovascular disease in patients with diabetes .3051 6.6.1. Principles of multifactorial management . .3062 6.1 Lifestyle . .3051 6.6.2. Gaps in knowledge . .3064 6.1.1. Diet . .3051 6.6.3. Recommendations for multifactorial risk management 6.1.2. Physical activity . .3052 in diabetes . .3064 6.1.3. Smoking . .3052 7. Management of stable and unstable coronary artery disease in 6.1.4. Gaps in knowledge . .3052 patients with diabetes . .3064 6.1.5. Recommendations on life style modifications in 7.1 Optimal medical treatment for patients with chronic diabetes . .3052 coronary artery disease and diabetes . .3064 ESC Guidelines 3037 7.1.1. Beta-adrenergic blockers . .3064 12.2 Gaps in Knowledge . .3082 7.1.2. Blockersof the renin-angiotensin-aldosterone system 3064 12.3 Recommendations for patient-centred care in diabetes .3082 7.1.3. Lipid-lowering drugs