It is commonly assumed that high oestradiol levels in women are cardioprotective. We assessed the association between oestradiol and the risk of incident myocardial infarction (MI) in women.
We used data from 263 295 female UK Biobank participants [mean age 56.2; standard deviation (SD) 8.0 years] without previous cardiovascular disease (CVD). Associations of oestradiol with age and other cardiovascular risk factors were assessed. Cox proportional hazards models estimated crude, ag- and multiple-adjusted hazard ratios (HR) for MI associated with oestradiol levels.
After a mean follow-up of 9 years, 2206 incident cases of MI had been recorded, including 230 events among the 57 204 women (mean age 48) with detectable oestradiol levels. In the unadjusted analyses, a unit higher in log-transformed oestradiol was associated with an HR [95% confidence interval (CI) for MI of 0.73 (0.58; 0.92)]. After adjusting for age, this HR became 0.94 (0.75; 1.17), and after further adjusting for classical CVD risk factors, it was 1.05 (0.83; 1.31. Results were similar in subgroup analyses defined by age, menopausal status, socioeconomic status, contraceptive pill use and the use of hormone replacement therapy. The multivariable-adjusted HR for the 171 431 women (mean age 59) with undetectable levels of oestradiol, compared with those with detectable levels, was 0.97 (0.92; 1.02).
Higher levels of oestradiol were not associated with a decreased risk of MI. The presumed cardioprotective effects of oestradiol seem to be largely confounded by age and further confounded by other cardiovascular risk factors.
Sex differences in the association between major and modifiable risk factors with cardiovascular disease
Most of the burden of cardiovascular diseases (CVD) is explained by a composite of physiological and lifestyle factors - chiefly, elevated blood pressure, obesity, diabetes, cigarette smoking, poor diet, and physical inactivity. There is increasing evidence that some of these risk factors have stronger effects on CVD in women than men. Although preventive strategies aimed at lowering the burden of these risk factors will benefit all, a sound knowledge of whether there are meaningful sex differences in relationships between traditional chronic disease risk factors and disease outcomes should help promote development of effective, sex-specific interventions. Addressing sex differences in relationships between risk factors and CVD risk is of importance from clinical and public health perspectives. Identifying significant sex differences in how risk factors relate to CVD risk should provide an impetus for targeted interventions aimed at reducing the prevalence of disease. Moreover, sex-specific estimates of disease risks associated with modifiable risk factors are essential for accurate estimation of the burden of disease due to these factors. These findings would help to inform the decision making process to maximize the efficacy of the allocation of health care resources, both in the UK and worldwide. Sex-specific estimates for the association between common lifestyle risk factors (elevated blood pressure, obesity, diabetes, cigarette smoking and a poor diet) and the risk of incident CVD will be determined. These sex-specific estimates will be used to evaluate whether or not the risk of stroke and coronary disease associated with these risk factors is similar between women and men. Analyses will be conducted in all individuals, as well as in subgroups defined by age, so as to identify sex-specific changes with ageing (for example, post-menopause), and socioeconomic status, to explore the effects of deprivation. Baseline and follow-up data on the full cohort of women and men in the UK Biobank, except those with pre-existing CVD at baseline, are requested.
|Lead investigator:||Professor Mark Woodward|
|Lead institution:||George Institute for Global Health|