Background: Previous evidence demonstrates an increased risk of incident cardiovascular disease (CVD) in women with early menopause and/or adverse pregnancy outcomes. It also suggests an inverse association between physical activity and risk of incident CVD. However, this association in women with novel risk factors have not been evaluated. Therefore, we aimed to address this hypothesis. Methods: We explored the data of 253,300 women without a history of CVD or life limiting conditions from the UK Biobank cohort, we further stratified women with a history of early menopause and/or complicated pregnancy to investigate how the risks affect indent CVD in women. We defined early menopause as any history of natural or surgical (bilateral oophorectomy) menopause < 47 years and adverse pregnancy outcomes as a history of gestational diabetes, hypertensive disorders of pregnancy, stillbirth or ? two miscarriages. We then classified women into three categories of physical activity based on their responses to the International Physical Activity Questionnaire. Women with a total MET-min/week of ? 3000, ? 600 and ? 600 were categorised into high, moderate, and low levels of physical activity, respectively. We also assessed the dose-response interaction between physical activity and risk of incident CVD (heart failure (HF), arrhythmia, coronary heart disease (CHD), and stroke) in our population and adjusted all the models for potential CVD risk factors. Results: During a median follow-up of 13 years, we found a significant increased risk of incident HF, arrhythmia and CHD in women with early menopause/complicated pregnancy, compared to women without these risk factors. Higher levels of physical activity reduced the risk of incident HF (HR 0.81, 95% CI 0.67 0.97) and arrhythmia (HR 0.84, 95% CI 0.75 0.94), compared to a low levels. Moreover, a moderate level of physical activity attenuated the risk of incident arrhythmia (HR 0.82, 95% CI 0.74 0.92). However, no significant associations were found between physical activity risk of incident stroke or CHD. Conclusion: Our study indicates that higher levels of PA significantly attenuate the risk of HF and arrhythmia in women with novel risk factors and should be recommended to women to reduce their increased risk of CVD.

The authors have declared no competing interest.

This study is related to the UKBiobank cohort study.

EJH was supported by an Australian National Heart Foundation Future Leader Fellowship (ID: 102536; 2020-2023).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The UK Biobank received ethical approval from the Northwest Multicentre Research Ethics Committee (11/NW/0382). All participants gave written informed consent. This study has been conducted using the UK Biobank Resource under application number 55469.

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This research was conducted using the UK Biobank Resource (http://www.ukbiobank.ac.uk/) under application 55469. Data from the UK Biobank is accessible to eligible researchers via applying to www.ukbiobank.ac.uk.