Cardiovascular risk trajectories in women with history of pregnancy complications

Preeclampsia, gestational hypertension, preterm delivery and fetal growth restriction are common pregnancy complications which each affect roughly 3 to 12 % of individual pregnancies. Growing evidence indicates that women with a history of these conditions are at increased risk of cardiovascular disease (CVD, such as myocardial infarction and stroke) compared with women with normal pregnancies. Recent guidelines for prevention of CVD recommend that selected pregnancy complications be screened to identify high-risk women for careful monitoring and control of risk factors for CVD such as high blood pressure and adverse lipid levels. Yet the current science gives scant foundation for recommending how information on CVD risk factors may be used to improve cardiovascular health in women. We have combined data on pregnancy history, CVD risk factors and CVD events for ~30,000 female participants in the HUNT Study. Participants' pregnancies have occurred since 1967, clinical examinations occurred up to three times between 1984 and 2008, and participants are followed in disease and mortality registries to 2015. With these longitudinal data, we determined the natural history of CVD risk factors as they emerge from before first pregnancy to 60 years of age. We quantified the associations of pregnancy complications with the risk of CVD events and determined the extent to which pregnancy complications improve the prediction of CVD. Our analyses of cardiovascular risk factor trajectories have shown that women with preeclampsia or gestational hypertension have an adverse cardiovascular risk factor profile already before pregnancy compared with normotensive women, and the differences persisted beyond 50 years of age. The adverse cardiovascular risk factor profile consisted of more adiposity and higher blood pressure, resting heart rate, serum lipids and glucose. The findings suggest that women with a history of hypertensive disorders in pregnancy may be expected to pass beyond treatment thresholds of cardiovascular risk factors at least 10 years earlier than women with normotensive pregnancy. We also observed that women with normotensive pregnancy had a decline in blood pressure from before to after pregnancy, and they thereafter had lower blood pressure for many years, compared with nulliparous women. This blood pressure reduction after pregnancy was small or absent in women with preeclampsia or gestational hypertension. We examined the association between pregnancy complications and cardiovascular disease and observed that women with hypertensive pregnancy complications had ~60% higher risk of cardiovascular disease compared with women with normotensive pregnancy. ~3/4 of this increased risk could be explained by higher blood pressure or adiposity. Information about pregnancy complications did not meaningfully improve cardiovascular risk prediction above and beyond conventional cardiovascular risk factors. We also examined whether the offspring born after complicated pregnancies carry adverse CVD risk factors in young adulthood. We found that people born after pregnancies with preeclampsia or hypertension have higher blood pressure and body mass index in young adulthood, compared with other young adults. However, this association was strongly attenuated when we adjusted for the mother's blood pressure and body mass index in our analyses. Further, in a sibling analysis we found that young adults born after pregnancy with preeclampsia or hypertension had similar blood pressure and body mass index as their sibling born after pregnancies without such complications. This suggests that the cardiovascular risk factors are explained by genes or lifestyle shared by the siblings, rather than an intrauterine effect. All children of mothers who have experienced preeclampsia or hypertension in pregnancy may be at increased risk of cardiovascular disease, not only those who were born after a complicated pregnancy.

The project has demonstrated how cardiovascular risk factors develop earlier in women with hypertensive disorders in pregnancy, and that elevated blood pressure and body mass likely explain approx. ¾ of their excess risk of cardiovascular events. This knowledge will likely guide future development of CVD prevention strategies for these women. Our finding that information on pregnancy complications does not meaningfully improve CVD prevention fills a knowledge gap that has been highlighted in recent CVD prevention guidelines. Our findings in the offspring exposed to hypertension in utero, indicating that their excess cardiovascular risk factors are explained by genetic or environmental factors shared by offspring of hypertensive pregnancies and their siblings, will likely guide our and other's future research in this field. For our research group, the project has resulted in novel method skills and international collaborations that are highly valuable for our future work.

Roughly a quarter of parous women will experience one of several pregnancy complications associated with elevated risk of cardiovascular disease (CVD) as they mature. These common pregnancy complications include the hypertensive disorders of pregnancy (pr eeclampsia and gestational hypertension), gestational diabetes, preterm delivery and fetal growth restriction. Growing evidence indicates that women with a history of these conditions are twice as likely to develop coronary heart disease and stroke than w omen with normal pregnancies. Recent guidelines for prevention of CVD recommend that selected pregnancy complications be screened to identify high-risk women for careful monitoring and control of cardiovascular disease (CVD) risk factors. Yet the current science gives scant foundation for recommending which CVD risk factors should be monitored, what screening schedule is optimal, or whether and how CVD risk prediction scores should incorporate pregnancy complications. We propose to combine data on pregn ancy history, clinical CVD risk factors measured three times over two decades, and CVD events for ~30,000 female participants in the HUNT Study. Participants' pregnancies have occurred since 1967, clinical examinations occurred three times between 1984 an d 2008, and participants can be followed in disease and mortality registries through 2011. With these unique longitudinal data, we can determine the natural history of CVD risk factors as they emerge for more than 40 years after common pregnancy complicat ions. We can quantify the associations of pregnancy complacations with the risk of CVD events and determine the extent to which pregnancy complications improve the prediction of CVD. The results will be directly and immediately applicable to improve the c linical care of millions of women whose pregnancy histories identify their high risk of CVD. By harnessing pregnancy history, we can better predict and prevent the leading causes of morbidity and mortality in women.