Association of menopausal characteristics and risk of coronary heart disease: A pan-European case-cohort analysis

Veerle Dam, Yvonne T. Van Der Schouw*, N. Charlotte Onland-Moret, Rolf H.H. Groenwold, Sanne A.E. Peters, Stephen Burgess, Angela M. Wood, Maria Dolores Chirlaque, Karel G.M. Moons, Clare Oliver-Williams, Ewoud Schuit, Kaja Tikk, Elisabete Weiderpass, Marianne Holm, Anne Tjønneland, Tilman Kühn, Renée T. Fortner, Antonia Trichopoulou, Anna Karakatsani, Carlo La VecchiaPietro Ferrari, Marc Gunter, Giovanna Masala, Sabina Sieri, Rosario Tumino, Salvatore Panico, Jolanda M.A. Boer, W. M. Monique Verschuren, Elena Salamanca-Fernández, Larraitz Arriola, Conchi Moreno-Iribas, Gunnar Engström, Olle Melander, Maria Nordendahl, Patrik Wennberg, Timothy J. Key, Sandra Colorado-Yohar, Giuseppe Matullo, Kim Overvad, Francoise Clavel-Chapelon, Heiner Boeing, J. Ramon Quiros, Emanuele Di Angelantonio, Claudia Langenberg, Michael J. Sweeting, Elio Riboli, Nicholas J. Wareham, John Danesh, Adam Butterworth

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors. Methods: We used data from EPIC-CVD, a case-cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders. Results: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01-1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10-1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96-1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors. Conclusions: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease.

Original languageEnglish
Article numberdyz016
Pages (from-to)1275-1285
Number of pages11
JournalInternational Journal of Epidemiology
Issue number4
Publication statusPublished - 1 Aug 2019
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the European Union Framework 7 (HEALTH-F2-2012–279233), the European Research Council (268834), the UK Medical Research Council (G0800270, MR/ L003120/1), the British Heart Foundation (SP/09/002, RG/08/014, RG13/13/30194) and the UK National Institute of Health Research (to EPIC-CVD). The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); Ministry of Health and Social Solidarity, Stavros Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council (UK). This work is supported by the Dutch Heart Foundation (2013T083 to V.D.). This work was supported by a UK Medical Research Council Skills Development Fellowship (MR/P014550/1 to S.A.E.P.). None of the funding sources had a role in the collection, analysis and interpretation of the data, nor in the decision to submit the article for publication.

Publisher Copyright:
© 2019 The Author(s).


  • ageing
  • coronary disease
  • Epidemiology
  • Menopause
  • risk factors
  • women


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