Association Between Physical Activity and Risk of Incident Cardiovascular Disease in Women with Novel Risk Factors: Evidence from the UK Biobank Cohort

Introduction: Early menopause and complicated pregnancy are associated with a higher risk of cardiovascular diseases (CVD), such as coronary heart disease (CHD) or heart failure (HF). Physical activity (PA) is a modifiable behaviour that typically reduces the risk of CVD; however, it is unclear if this is the case for these novel risk factors. Hypothesis: We hypothesised that PA could moderate the risk of incident CVD in women with novel risk factors. Aims: This study sought to investigate the effect of PA on the risk of incident CVD in women with a history of early menopause and/or complicated pregnancy. Methods: We included 55,930 women (median age 59) with novel risk factors and free from CVD (HF, CHD, arrhythmia, and ischemic stroke) from the UK Biobank Study. Novel risk factors were defined as complicated pregnancy (n=23,627, median age=56), described as a history of any stillbirth or ≥2 miscarriages, gestational diabetes, or hypertensive disorders of pregnancy, and early menopause (n=35,838, median age=60), defined as natural or surgical (bilateral oophorectomy) menopause <47age. Women were categorised into three groups of high (≥1,500 MET-minutes/week), moderate (≥600 MET-minutes/week) and low levels of PA according to their responses to the International Physical Activity Questionnaire (IPAQ). Multivariable Cox proportional hazard models were performed, and the results were adjusted for traditional CVD risk factors such as smoking, alcohol consumption, obesity, diabetes, hypertension, hyperlipidaemia, and cancer. Results: At a median follow-up of 13 years, there were 6636 events. A high level of PA was significantly associated with a lower risk of incident HF (hazard ratio [HR] 0.76, 95% CI[0.63 0.90], n= 1374), arrhythmia (HR 0.79, 95% CI[0.70 0.88], n=2699), and stroke (HR 0.77, 95% CI[0.61 0.97], n=797), compared to low levels of PA. We also observed a significant association between moderate levels of PA and reduced risk of incident arrhythmia (hazard ratio 0.78, 95% CI 0.70 0.87) compared to low levels of PA. Conclusion: High levels of PA can significantly reduce the risk of most incidents of CVD in women with novel risk factors. Thus, higher PA should be strongly encouraged to women with novel risk factors to lower the risk of CVD.