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

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Abstract

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
Pages (from-to)1275-1285
JournalInternational Journal of Epidemiology
Volume48
Issue number4
Early online date22 Feb 2019
DOIs
Publication statusPublished - 01 Aug 2019
Externally publishedYes

Bibliographical note

© The Author(s) 2019. Published by Oxford University Press on behalf of the International Epidemiological Association.

Keywords

  • Adult
  • Age Factors
  • Cohort Studies
  • Coronary Disease/epidemiology
  • Europe/epidemiology
  • Female
  • Humans
  • Menopause
  • Middle Aged
  • Ovariectomy/adverse effects
  • Proportional Hazards Models
  • Risk Factors

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  • Cite this

    Dam, V., van der Schouw, Y. T., Onland-Moret, N. C., Groenwold, R. H. H., Peters, S. A. E., Burgess, S., Wood, A. M., Chirlaque, M-D., Moons, K. G. M., Oliver-Williams, C., Schuit, E., Tikk, K., Weiderpass, E., Holm, M., Tjønneland, A., Kühn, T., Fortner, R. T., Trichopoulou, A., Karakatsani, A., ... Butterworth, A. (2019). Association of menopausal characteristics and risk of coronary heart disease: a pan-European case-cohort analysis. International Journal of Epidemiology, 48(4), 1275-1285. https://doi.org/10.1093/ije/dyz016