Pre-eclampsia and increased cardiovascular risk

Cardiovascular disease is the leading cause of death in women.1 Although its incidence is declining in men, this is not the case in women.2

Pre-eclampsia is a novel cardiovascular risk marker. Pre-eclampsia increases both the long term risk of cardiovascular disease and the risk that it will occur earlier. This has been shown consistently over time, in different settings, and for coronary and cerebrovascular outcomes. The magnitude of the risk for cardiovascular disease in women with previous pre-eclampsia is similar to that of dysplipidaemia.3 Risk seems to be greater for pre-eclampsia than for gestational (or “pregnancy induced”, non-proteinuric) hypertension. Risk is also greater for early-onset pre-eclampsia and for pre-eclampsia associated with placental complications (such as stillbirth or small for gestational age infants).4 Two papers in this week's BMJ assess the link between pre-eclampsia and cardiovascular disease.5 6

In the first paper, Bellamy and colleagues summarise the consistency and strength of the association between pre-eclampsia and long term risk of cardiovascular disease.5 They confirm the dose-response relation between severe pre-eclampsia (more severe hypertension or pre-eclampsia of earlier onset) and cardiovascular disease, as well as between gestational hypertension and long term hypertension.

The underlying link between pre-eclampsia and cardiovascular disease is unclear. Although pre-eclampsia may initiate endothelial damage, it is thought to be more likely that pre-eclampsia and cardiovascular disease have a common pathogenesis rooted in shared risk markers. Women with previous pre-eclampsia more often have the metabolic syndrome or its components (such as overweight or obesity, dyslipidaemia, hypertension, or insulin resistance).7 In the second paper, Magnussen and colleagues provide support for a shared pathogenesis between cardiovascular disease and pre-eclampsia.6 In their linkage study of Norway's medical birth registry and a Norwegian population based study of cardiovascular risk markers, they found significant associations (after adjustment) between pre-eclampsia and higher waist circumference, systolic blood pressure, diastolic blood pressure, and non-fasting total cholesterol before pregnancy.6

Despite the important attributable risk of cardiovascular disease associated with pre-eclampsia, the absolute risk over the short term is low.8 Bellamy and colleagues show that in the 10-15 years after pre-eclampsia, the risk of cardiovascular disease and death is low (hypertension 21.9%, ischaemic heart disease 0.2%, stroke 0.2%, venous thromboembolic disease 0.3%, death 1.4%). Given these low short term risks, few women with previous pre-eclampsia are likely to have absolute values of lipids, blood pressure, or blood sugar that are above intervention thresholds, according to existing guidelines.

What should clinicians do for women who have had pre-eclampsia? Firstly, we must recognise that these women are still young, their absolute risk of cardiovascular disease is low over the short term, and their risk will evolve over subsequent decades. As such, we have an opportunity for primary prevention, especially as cardiovascular disease is largely preventable. In a large multinational study, 90% of the risk of a first myocardial infarction was accounted for by nine potentially modifiable risk markers: smoking, dyslipidaemia, hypertension, diabetes, abdominal obesity, psychosocial factors, inadequate consumption of fruits and vegetables, insufficient regular consumption of alcohol, and lack of exercise.9

Secondly, although guidelines on thresholds and targets for the treatment of hypertension, diabetes, and dyslipidaemia rely heavily on estimates of short term cardiovascular risk, those thresholds and targets vary widely.10 Global assessment tools for cardiovascular risk (like Framingham) have limited applicability to young women. Limitations include errors in the risk estimate at the extreme ranges and omission of traditional (for example, obesity) or novel (for example, microalbuminuria) risk markers of cardiovascular disease.11

In terms of action, several possibilities exist. If we consider earlier screening for traditional risk markers of cardiovascular disease or lower treatment thresholds and targets (or both), no evidence is currently available to guide our decision making. If we consider following existing recommendations for screening or treatment (or both), we have a large body of evidence showing that a heart-healthy diet and lifestyle decreases cardiovascular risk.1 Such advice is applicable to all women—regardless of risk of cardiovascular disease—and it is probably the most appropriate initial intervention for women with previous pre-eclampsia.

Unfortunately, simply advising people to undertake a healthier lifestyle is not enough to change their behaviour. However, women might be more receptive if they have had a complicated pregnancy. Perhaps we could tailor the advice to women with newborns and young children. We know that the new mothers' caregiving role is one of the most commonly reported reasons for lack of activity among women,12 and this extends to the presence of other (older) children in the household.13

We should ask women about their pregnancy experience. Women with a history of pre-eclampsia (or gestational hypertension) should have their risk of cardiovascular disease actively assessed at three to six months postpartum. They should pursue a heart-healthy diet and lifestyle. All of these women should probably be screened early for traditional risk markers of cardiovascular disease, and they should be treated, at a minimum, according to published guidelines. Future research must investigate whether targeting women with previous pre-eclampsia identifies a population that is more receptive to lifestyle changes or one that should have their traditional cardiovascular risk markers treated earlier and more aggressively (or both).