Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women
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Age at Menopause and the Risk of Stroke : Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women. / Tschiderer, Lena; Peters, Sanne A.E.; van der Schouw, Yvonne T.; van Westing, Anniek C.; Tong, Tammy Y.N.; Willeit, Peter; Seekircher, Lisa; Moreno-Iribas, Conchi; Huerta, José María; Crous-Bou, Marta; Söderholm, Martin; Schulze, Matthias B.; Johansson, Cecilia; Själander, Sara; Heath, Alicia K.; Macciotta, Alessandra; Dahm, Christina C.; Ibsen, Daniel B.; Pala, Valeria; Mellemkjær, Lene; Burgess, Stephen; Wood, Angela; Kaaks, Rudolf; Katzke, Verena; Amiano, Pilar; Rodriguez-Barranco, Miguel; Engström, Gunnar; Weiderpass, Elisabete; Tjønneland, Anne; Halkjær, Jytte; Panico, Salvatore; Danesh, John; Butterworth, Adam; Onland-Moret, N. Charlotte.
In: Journal of the American Heart Association, Vol. 12, No. 18, e030280, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Age at Menopause and the Risk of Stroke
T2 - Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women
AU - Tschiderer, Lena
AU - Peters, Sanne A.E.
AU - van der Schouw, Yvonne T.
AU - van Westing, Anniek C.
AU - Tong, Tammy Y.N.
AU - Willeit, Peter
AU - Seekircher, Lisa
AU - Moreno-Iribas, Conchi
AU - Huerta, José María
AU - Crous-Bou, Marta
AU - Söderholm, Martin
AU - Schulze, Matthias B.
AU - Johansson, Cecilia
AU - Själander, Sara
AU - Heath, Alicia K.
AU - Macciotta, Alessandra
AU - Dahm, Christina C.
AU - Ibsen, Daniel B.
AU - Pala, Valeria
AU - Mellemkjær, Lene
AU - Burgess, Stephen
AU - Wood, Angela
AU - Kaaks, Rudolf
AU - Katzke, Verena
AU - Amiano, Pilar
AU - Rodriguez-Barranco, Miguel
AU - Engström, Gunnar
AU - Weiderpass, Elisabete
AU - Tjønneland, Anne
AU - Halkjær, Jytte
AU - Panico, Salvatore
AU - Danesh, John
AU - Butterworth, Adam
AU - Onland-Moret, N. Charlotte
N1 - Publisher Copyright: © 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2023
Y1 - 2023
N2 - BACKGROUND: Observational studies have shown that women with an early menopause are at higher risk of stroke compared with 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 (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8–13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07–1.12) for stroke, 1.09 (95% CI, 1.06–1.13) for ischemic stroke, 1.10 (95% CI, 1.04–1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08–1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84–1.20) for subarachnoid hemorrhage. When using 2-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.
AB - BACKGROUND: Observational studies have shown that women with an early menopause are at higher risk of stroke compared with 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 (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8–13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07–1.12) for stroke, 1.09 (95% CI, 1.06–1.13) for ischemic stroke, 1.10 (95% CI, 1.04–1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08–1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84–1.20) for subarachnoid hemorrhage. When using 2-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.
KW - age at menopause
KW - Mendelian randomization analysis
KW - observational analysis
KW - stroke
U2 - 10.1161/JAHA.123.030280
DO - 10.1161/JAHA.123.030280
M3 - Journal article
C2 - 37681566
AN - SCOPUS:85171770875
VL - 12
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
SN - 2047-9980
IS - 18
M1 - e030280
ER -
ID: 375961341