Hypertensive disorders in pregnancy and ischemic heart disease in later life

A number of studies have demonstrated associations between a diagnosis of pre-eclampsia in pregnancy and ischemic heart disease (IHD) in later life. This association is plausible given the evidence outlined above for a relationship with hypertension, which is a well-recognized risk factor for IHD. However, IHD is relatively uncommon in young women. Consequently, the most feasible studies for addressing this question are register-based studies, since these can include a sufficient number of women to be powered to address the research question. In all but one of these studies, however, the definition of exposure is based on the coding of clinical records, which is open to misclassification.

The analysis of controls for the oral contraception cohort, reported by Hannaford and described above, reported relative risks of 1.5—2.2 for a number of different IHD conditions. The association persisted when the analysis was stratified by chronic hypertension and the analysis was adjusted for age, smoking and social class (Hannaford et al., 1997). A national retrospective cohort study of 129,920 women having first births in Scotland between 1980 and 1984 demonstrated an approximately twofold risk of death or hospital admission due to IHD in relation to a diagnosis of pre-eclampsia (Smith etal., 2001). The diagnosis of pre-eclampsia was based on coding in a maternity register and 18% of women were documented as experiencing pre-eclampsia, indicating that the diagnostic criteria were relatively broad. The association was not attenuated by adjusting for maternal age, social deprivation, height or essential hypertension. Smoking data were lacking in this cohort but it is unlikely that smoking might have explained the observed association since pre-eclampsia is less common among smokers (England et al., 2002). A national registry based study in Denmark of over 600,000 births also demonstrated an increased risk of death due to cardiovascular causes (Irgens et al., 2001). These authors demonstrated that the relative risk of death associated with a diagnosis of pre-eclampsia varied in relation to gestational age. For term births the relative risk was 1.6 and for preterm births it was 8.1. However, previous studies have shown that preterm birth is a risk factor for IHD independently of pre-eclampsia (Smith et al., 2001, 2000). Irgens et al. did not perform a formal statistical test for interaction.

Each of these large-scale studies supports the hypothesis that a diagnosis of pre-eclampsia is associated with an increased risk of later IHD. However, in all studies the accuracy of diagnosis is debatable as they are based on large-scale registers of case note data. A single large-scale study has been described with well-defined data on the diagnosis of pre-eclampsia (Wilson et al., 2003), the Aberdeen study described above. This study generated somewhat inconsistent results. There was a twofold risk of death due to IHD on the basis of record linking to death certificate data although due to small numbers this was of borderline statistical significance (P — 0.09). Surprisingly, there was no trend of an increased risk of hospital admission for IHD (relative risk 0.9, upper 95% CI 1.4). However, there was no association between gestational hypertension and either hospital admission or death due to IHD. In the presence of these inconsistencies, further work will be required to define the strength and nature of the association, if any, between hypertensive disorders in pregnancy and later risk of IHD.

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