Age at Menopause and the Risk of Stroke : Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women
(2023) In Journal of the American Heart Association 12(18).- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2023-09-19
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- age at menopause, Mendelian randomization analysis, observational analysis, stroke
- in
- Journal of the American Heart Association
- volume
- 12
- issue
- 18
- article number
- e030280
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:37681566
- scopus:85171770875
- ISSN
- 2047-9980
- DOI
- 10.1161/JAHA.123.030280
- language
- English
- LU publication?
- yes
- id
- ba278b27-371f-400f-a562-eace75e61842
- date added to LUP
- 2023-12-13 14:58:39
- date last changed
- 2024-04-12 06:47:11
@article{ba278b27-371f-400f-a562-eace75e61842,
abstract = {{<p>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.</p>}},
author = {{Tschiderer, Lena and Peters, Sanne A. E. and van der Schouw, Yvonne T. and van Westing, Anniek C. and Tong, Tammy Y.N. and Willeit, Peter and Seekircher, Lisa and Moreno-Iribas, Conchi and Huerta, José María and Crous-Bou, Marta and Söderholm, Martin and Schulze, Matthias B. and Johansson, Cecilia and Själander, Sara and Heath, Alicia K. and Macciotta, Alessandra and Dahm, Christina C. and Ibsen, Daniel B. and Pala, Valeria and Mellemkjær, Lene and Burgess, Stephen and Wood, Angela and Kaaks, Rudolf and Katzke, Verena and Amiano, Pilar and Rodriguez-Barranco, Miguel and Engström, Gunnar and Weiderpass, Elisabete and Tjønneland, Anne and Halkjær, Jytte and Panico, Salvatore and Danesh, John and Butterworth, Adam and Onland-Moret, N. Charlotte}},
issn = {{2047-9980}},
keywords = {{age at menopause; Mendelian randomization analysis; observational analysis; stroke}},
language = {{eng}},
month = {{09}},
number = {{18}},
publisher = {{Wiley-Blackwell}},
series = {{Journal of the American Heart Association}},
title = {{Age at Menopause and the Risk of Stroke : Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women}},
url = {{http://dx.doi.org/10.1161/JAHA.123.030280}},
doi = {{10.1161/JAHA.123.030280}},
volume = {{12}},
year = {{2023}},
}