"This is a man's world..." : Cardiovascular disease in women: female-specific risk factors and risk prediction

Abstract

Cardiovascular disease (CVD) is still the leading cause of death in both sexes in Western countries with 17.7 million deaths worldwide in 2015. Sex differences are recognized more often and incidence rates show that women accounted for more new cases of CVD compared to men. Studies also show that women have similar risk factors compared to men, although their impact is different for some in women. Furthermore, female-specific risk factors receive increasing attention in cardiovascular research. This thesis aimed to study whether female-specific risk factors (menopausal status, age at menopause, vasomotor menopausal symptoms and polycystic ovary syndrome) are (causally) associated with CVD, coronary heart disease (CHD) and stroke and to assess the availability and performance of existing CVD risk prediction models for women in the general population and to establish whether the performance of a subset of these models differs between women with and without a history of hypertensive disorders of pregnancy. Our observational findings on menopause support the general believe that women have an unfavourable cardiovascular risk profile around and after menopause and that CHD risk in women increases after menopause. However, our Mendelian Randomization study showed that the association between menopause and CHD risk is likely not causal. Additionally, we did not find associations for vasomotor menopausal symptoms and polycystic ovary syndrome, and thus literature on these risk factors remains inconclusive. Therefore, it will be worthwhile to also conduct MR studies on these and other female-specific risk factors to establish causality. Although the causes and mechanisms underlying CVD risk in women are not fully understood yet, it is evident that also in women CVD is an important cause of morbidity and mortality. Therefore, it is important that we identify women at high risk and implement preventive measures when necessary. In our review we showed that an abundance of cardiovascular risk prediction models is available for the general population and many of them are developed specifically for women or included sex as a predictor. Most of these models have moderately to good performance and it has been thought that these models could improve by adding female-specific risk factors. However, several studies that implemented this method, could not confirm this hypothesis. When applying the well-known CVD risk prediction models in women with hypertensive disorders of pregnancy, they do predict higher absolute cardiovascular risks compared to women with normal pregnancies. Thus, these women might benefit from close monitoring or screening for CVD as is also advised in the American guideline for the prevention of cardiovascular disease in women. We showed that the well-known models used in the general population can also be used in women with hypertensive disorders of pregnancy and no separate model for women with hypertensive disorders of pregnancy is necessary.