Reassessing the association between age at menarche and cardiovascular disease: observational and Mendelian randomization analyses
Main finding · MIResult — go to the resultHazard ratio 0.92 95% CI 0.86–0.99Authors' conclusion
This study supported non-linear observational associations between AAM and MI and ischaemic stroke. MR analyses suggested a causal relationship between higher AAM and risk of MI without an indication for non-linearity. There was no support for a potential causal link with ischaemic and haemorrhagic stroke.
Study context
- Population
- Women without pre-existing myocardial infarction (MI) or stroke at baseline, EPIC-CVD and UK BiobankEPIC-CVD and UK Biobank
- Participants
- 283,210 women
- Exposure
- Age at menarche
- Outcome
- Incident MI, ischaemic and haemorrhagic stroke later in life
Methodological detailsobservational and Mendelian randomization analyses, non-linear Mendelian randomization (MR) (fractional polynomials), linear MR (inverse-variance weighted)
- Observational and Mendelian randomization analyses
- Non-linear MR (fractional polynomials)
- Linear MR (inverse-variance weighted)
Main finding
MI
Hazard ratio
0.92
95% CI 0.86–0.99
Each year higher genetically proxied AAM
HR 0.92 (95% CI 0.86–0.99)
Each year higher genetically proxied AAM, as printed
As reported in the abstract
Observational data: associations, not effects.
Further findings
Observational association of age at menarche (AAM) with MI and ischaemic stroke
- U-shaped: higher risks at AAM ≤12 and ≥16 vs 13 years
Events
- MI
- 8468
- Ischaemic stroke
- 5501
- Haemorrhagic stroke
- 1887
- Median AAM, years (IQR 12-14)
- 13
Original publication
Reassessing the association between age at menarche and cardiovascular disease: observational and Mendelian randomization analyses. Eur J Prev Cardiol. Published 18 March 2025. doi:10.
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