Age at menopause and the risk of stroke: Observational and Mendelian Randomization analysis in 204,244 postmenopausal women Journal of the American Heart Association
Abstract Methods Outcome definition Results Discussion Strengths and limitations Implications of the findings Conclusion Supplementary Material Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared to women with a later menopause. However, associations with stroke subtypes are inconsistent and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD study. A total of 204,244 postmenopausal women without a history of stroke at baseline were included (7,883 from EPIC-CVD [5,292 from the sub-cohort]; 196,361 from the UK Biobank). Pooled mean baseline age was 58.9 years (standard deviation 5.8) and pooled mean age at menopause was 47.8 years (standard deviation 6.2). Over a median follow-up of 12.6 years (interquartile range 11.8, 13.3), 6,770 women experienced a stroke (5,155 ischemic strokes, 1,615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox-regression analyses, the pooled hazard ratios per five years younger age at menopause were 1.09 (95% confidence interval: 1.07, 1.12) for stroke, 1.09 (1.06, 1.13) for ischemic stroke, 1.10 (1.04, 1.16) for hemorrhagic stroke, 1.14 (1.08, 1.20) for intracerebral hemorrhage, and 1.00 (0.84, 1.20) for subarachnoid hemorrhage. When using two-sample Mendelian Randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. Conclusions In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.
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Lena Tschiderer, Sanne AE Peters, Yvonne T van der Schouw et al.. Age at menopause and the risk of stroke: Observational and Mendelian Randomization analysis in 204,244 postmenopausal women. Journal of the American Heart Association. (2023). https://doi.org/10.1161/JAHA.123.030280 Lena Tschiderer, Sanne AE Peters, Yvonne T van der Schouw, Anniek C van Westing, Tammy YN Tong, Peter Willeit, Lisa Seekircher, Conchi Moreno-Iribas, José María Huerta, Marta Crous-Bou, Martin Söderholm, Matthias B Schulze, Cecilia Johansson, Sara Själander, Alicia K Heath, Alessandra Macciotta, Christina C Dahm, Daniel B Ibsen, Valeria Pala, Lene Mellemkjær, Stephen Burgess, Angela Wood, Rudolf Kaaks, Verena Katzke, Pilar Amiano, Miguel Rodriguez-Barranco, Gunnar Engström, Elisabete Weiderpass, Anne Tjønneland, Jytte Halkjær, Salvatore Panico, John Danesh, Adam Butterworth, N Charlotte Onland-Moret
1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands 2Institute of Health Economics, Medical University of Innsbruck, Innsbruck, Austria 3The George Institute for Global Health, School of Public Health, Imperial College London, London, United Kingdom 4The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia 5Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands 6Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, United Kingdom 7department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom 8Instituto de Salud Pública y Laboral de Navarra, 31003 Pamplona, Spain 9Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain 10Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain 11Department of Epidemiology, Murcia Regional Health Council- IMIB, Murcia, Spain 12Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO) - Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona 08908, Spain 13Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA 14Department of Neurology, Skåne University Hospital, Lund and Malmö, Malmö, Sweden 15Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden 16Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany 17Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany 18Skellefteå Research Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Västerbotten, Sweden 19Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden 20Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom 21Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, Turin, Italy 22Department of Public Health, Aarhus University, Aarhus, Denmark 23Steno Diabetes Center Aarhus, Aarhus, Denmark 24MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom 25Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark 26Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy 27Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark 28Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom 29MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom 30Division of Cancer Epidemiology, German Cancer Research Center, DKFZ, 69120 Heidelberg, Germany 31Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain 32Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastian, Spain 33Escuela Andaluza de Salud Pública (EASP), 18011 Granada, Spain 34Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain 35International Agency for Research on Cancer, World Health Organization, Lyon, France 36Department of Public Health, Section of Environmental Health, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, Denmark 37School of Medicine, Federico II University, Naples, Italy 38BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom 39National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge University Hospitals, Cambridge, United Kingdom 40The National Institute for Health and Care Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom 41Human Genetics, Wellcome Sanger Institute, Saffron Walden, United Kingdom 42Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, United Kingdom 43British Heart Foundation Centre of Research Excellence, Division of Cardiovascular Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom 44NIHR Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, United Kingdom 45BHF Centre of Research Excellence, School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom 