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Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke: EPIC-CVD case-cohort study

BMJ 2018; 361 doi: (Published 29 May 2018) Cite this as: BMJ 2018;361:k934
  1. Cristian Ricci, statistician12,
  2. Angela Wood, senior lecturer3,
  3. David Muller, research fellow4,
  4. Marc J Gunter, section head5,
  5. Antonio Agudo, unit head6,
  6. Heiner Boeing, professor7,
  7. Yvonne T van der Schouw, professor8,
  8. Samantha Warnakula, scientist3,
  9. Calogero Saieva, scientist9,
  10. Annemieke Spijkerman, senior scientist10,
  11. Ivonne Sluijs, assistant professor8,
  12. Anne Tjønneland, research head11,
  13. Cecilie Kyrø, postdoctoral researcher11,
  14. Elisabete Weiderpass, professor1215,
  15. Tilman Kühn, group head16,
  16. Rudolf Kaaks, professor16,
  17. Maria-Jose Sánchez, scientist1718,
  18. Salvatore Panico, professor19,
  19. Claudia Agnoli, scientist20,
  20. Domenico Palli, unit head9,
  21. Rosario Tumino, pathologist21,
  22. Gunnar Engström, professor22,
  23. Olle Melander, professor22,
  24. Fabrice Bonnet, professor23,
  25. Jolanda M A Boer, senior epidemiologist10,
  26. Timothy J Key, professor24,
  27. Ruth C Travis, associate professor24,
  28. Kim Overvad, professor2526,
  29. W M Monique Verschuren, professor810,
  30. J Ramón Quirós, unit head27,
  31. Antonia Trichopoulou, professor2829,
  32. Eleni-Maria Papatesta, scientist29,
  33. Eleni Peppa, nutritionist28,
  34. Conchi Moreno Iribas, senior epidemiologist3031,
  35. Diana Gavrila, senior epidemiologist1832,
  36. Ann-Sofie Forslund, scientist33,
  37. Jan-Håkan Jansson, scientist34,
  38. Giuseppe Matullo, associate professor35,
  39. Larraitz Arriola, epidemiologist36,
  40. Heinz Freisling, scientist1,
  41. Camille Lassale, research associate437,
  42. Ioanna Tzoulaki, reader438,
  43. Stephen J Sharp, senior statistician39,
  44. Nita G Forouhi, group leader39,
  45. Claudia Langenberg, group leader39,
  46. Rodolfo Saracci, professor1,
  47. Michael Sweeting, senior research associate3,
  48. Paul Brennan, section head40,
  49. Adam S Butterworth, lecturer3,
  50. Elio Riboli, chair4,
  51. Nick J Wareham, unit director39,
  52. John Danesh, professor3,
  53. Pietro Ferrari, group head1
  1. 1Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer, World Health Organization, 150 cours Albert Thomas, 69372 Lyon CEDEX 08, France
  2. 2Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa
  3. 3Medical Research Council, British Heart Foundation, Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  4. 4Department Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
  5. 5Nutritional Epidemiology Group, Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
  6. 6Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Barcelona, Spain
  7. 7Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
  8. 8Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
  9. 9Cancer Risk Factors and Lifestyle Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy
  10. 10Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Bilthoven, Netherlands
  11. 11Danish Cancer Society Research Center, Copenhagen, Denmark
  12. 12Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
  13. 13Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway
  14. 14Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  15. 15Genetic Epidemiology Group, Folkhälsan Research Center and Faculty of Medicine, University of Helsinki, Helsinki, Finland
  16. 16Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
  17. 17Andaluzian School of Public Health, University of Granada, Granada, Spain
  18. 18Biomedical Research Networking Center for Epidemiology and Public Health (CIBERESP), Madrid, Spain
  19. 19Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
  20. 20Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 
  21. 21Cancer Registry and Histopathology Department, Civic M P Arezzo Hospital, Ragusa, Italy
  22. 22Department of Clinical Sciences, Lund University, Malmö, Sweden
  23. 23Rennes University Hospital, Rennes, France
  24. 24Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  25. 25Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark
  26. 26Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
  27. 27Public Health Directorate of Asturias, Oviedo, Spain
  28. 28Hellenic Health Foundation, Athens, Greece
  29. 29WHO Collaborating Centre for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, University of Athens Medical School, Athens, Greece
  30. 30Navarre Public Health Institute, Institute for Health Research (IdiSNA), Pamplona, Spain
  31. 31Research Network in Health Services in Chronic Diseases (REDISSEC), Pamplona, Spain
  32. 32Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
  33. 33Department of Public Health and Clinical Medicine, Sunderby Research Unit, Umeå University, Umeå, Sweden
  34. 34Department of Public Health and Clinical Medicine, Skellefteå Research Unit, Department of Medicine, Umeå University, Umeå, Sweden
  35. 35Department Medical Sciences, University of Torino, Italian Institute for Genomic Medicine -IIGM/HuGeF, Torino, Italy
  36. 36Public Health Division of Gipuzkoa, Instituto BIO-Donostia, Basque Government, Gipuzkoa, Spain
  37. 37Department of Epidemiology and Public Health, University College London, London, UK
  38. 38Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
  39. 39Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, UK
  40. 40Genetic Epidemiology Group, Genetics Section, International Agency for Research on Cancer, Lyon, France
  1. Correspondence to: P Ferrari ferrarip{at}
  • Accepted 17 April 2018


Objective To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke.

Design Multicentre case-cohort study.

Setting A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries.

Participants 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison.

Main outcome measures Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke).

Results There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events.

Conclusions Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.


  • Contributors: AA, HB, AT, EW, RK, MS, SP, DP, RT, TJK, RCT, KO, WMMV, JRQ, AT, PM, LA, RS, NJW, ER, PF and JD collected, stored, and administered study participants’ information on lifestyle exposure within the EPIC study. NJW, CL, NGF, SJS, ASB, MS, ER, and JD designed the case-cohort study, and assessed and validated the cardiovascular disease (CVD) events within the EPIC-CVD study. CR, AMW, DM, MS, ASB, and PF performed the statistical analyses. CR, AMW, DM, MS, ASB, PF, RS, MJG, PB, and HF interpreted the results and prepared the first versions of the manuscript. All authors actively contributed to the final manuscript. PF is the guarantor.

  • Funding: This work was supported by the Direction Générale de la Santé (French Ministry of Health) (grant GR-IARC-2003-09-12-01). EPIC-CVD has been supported by the European Union Framework 7 (HEALTH-F2-2012-279233), the European Research Council (268834), the UK Medical Research Council (G0800270 and MR/L003120/1), the British Heart Foundation (SP/09/002 and RG/08/014 and RG13/13/30194), and the UK National Institute of Health Research. The establishment of the random subcohort was supported by the EU Sixth Framework Programme (FP6) (grant LSHM_CT_2006_037197 to the InterAct project) and the Medical Research Council Epidemiology Unit (grants MC_UU_12015/1 and MC_UU_12015/5).

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The ethical review boards of the International Agency for Research on Cancer and all local institutions where participants had been recruited gave approval for the study. All participants gave written informed consent.

  • Data sharing: Access to EPIC data and biospecimens can be found at

  • Transparency: The manuscripts’ guarantor (PF) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

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