Cardiovascular disease is the cause of death of 32% of women in the Netherlands . Not all women are at the same risk of cardiovascular disease. Prediction of risk in younger women is particularly difficult due to low sensitive and specific tests for these women. Identification of individual women at higher risk is a challenge. This proposal takes an innovative angle to gain insight in cardiovascular morbidity and mortality later in life in women using pregnancy related hypertensive complications. Approximately 10% to 15% of all pregnancies are complicated by hypertension and largely contribute to maternal and neonatal morbidity and mortality worldwide. In the Netherlands it is the largest single cause of maternal mortality . The vast majority of hypertensive disorders present themselves after 36 weeks of gestation . Therefore, we focus in this study on those women with pregnancy related hypertensive complications (near) at term (> 36 weeks gestation).
The etiology of hypertensive disorders of pregnancy is not fully understood, but the causal treatment is delivery of the baby and the placenta. Recently it was shown that in women at term with gestational hypertension or preeclampsia induction of labor is advisable to avoid progression to more severe disease . However, the health status of these women after pregnancy has been given little of any attention in routine clinical practice up to now. Obstetricians and midwifes are traditionally completely focused on pregnancy outcome and do not seem to bother about the significance of complications of pregnancy for the future health of the mother, this is also true for general practitioners.
Recently, data from epidemiologic studies incited the novel concept of pregnancy as cardiovascular challenge test; women who have had a pregnancy complicated by hypertensive disorders are prone to develop cardiovascular disease in later life [5–10]. In line with this concept is that pregnancy acts as a metabolic and cardiovascular stress test for the mother. During pregnancy a failure to meet the physiological demands will unmask impaired organ function, e.g. hypertension will arise and most often subside after delivery. However, these failures will remanifest in later life when the cumulative effects of ageing diminish the reserves of an already vulnerable (organ) system . Jonsdottir et al. examined causes of death in 374 women with a history of hypertensive complications in pregnancy and noted that their death rate from complications of coronary heart disease was significantly higher than expected from analysis of population data .
This concept is further supported by case-control studies by others and ourselves, demonstrating that women with a history of early preeclampsia have higher circulating concentrations of fasting insulin, lipid and coagulations factors post partum than controls matched for body mass index [12, 13]. These changes in vascular risk markers in women with a history of preeclampsia are part of the spectrum of the metabolic syndrome. The metabolic syndrome is hypothesised to be a key factor underlying cardiovascular disease and in particular coronary heart disease.
The mechanism of the link between preeclampsia and cardiovascular disease has not been clarified. Hypertensive disorders in pregnancy and cardiovascular disease may develop by common pathophysiologic pathways initiated by similar risk factors. Permanent vascular damage may occur during preeclampsia or gestational hypertension and subsequently contributes to the development of cardiovascular disease in later life, or cardiovascular disease is already present before pregnancy. However, determinants or risk indicators to be measured after pregnancy which would predict cardiovascular disease are lacking. Such risk indicators may identify women at risk at an early stage for them to benefit from intervention.
The concept described above is based on studies focusing on early, severe preeclampsia, which is a relatively rare disorder , while preeclampsia at (near) term is mostly mild and more common (75% of cases) . Therefore, prospective evaluation of those women is required to identify cardiovascular risk indicators after hypertensive pregnancy complications at term, with the eventual aim to offer these women the opportunity for primary prevention at a relatively young age .
We propose a cohort study to establish whether women with gestational hypertension or preeclampsia at term are at increased risk for cardiovascular disease in later life, and if these women are likely to benefit from tailored preventative interventions directed at modifiable cardiovascular risk indicators at a relative young age.