Pregnancy disorders and cardiovascular disease risk

Abstract

Cardiovascular disease is the most important cause of death in women in the Netherlands. Early identification of women at increased risk of cardiovascular disease and subsequent detection and treatment of risk factors contributes to the reduction of cardiovascular disease morbidity and mortality. A growing body of evidence indicates that women with a pregnancy disorder are at increased risk of developing cardiovascular disease later in life. Part I of this thesis focuses on causes of preterm delivery. In a systematic review we show that both high and low maternal total cholesterol and high triglyceride levels are associated with a significant increased risk of spontaneous preterm delivery, although this result could not be reproduced by all studies. In a cohort study of women with spontaneous preterm delivery, lower levels of total cholesterol and LDL-c, and higher levels of nonfasting glucose were found shortly after delivery as compared to women who deliver at term, yet these levels are still within a normal range. In the same cohort, the prevalence of previously undiagnosed congenital heart defects is approximately 5 times higher as compared to the general adult population. Part 2 of this thesis focuses on consequences of pregnancy disorders. In a large cohort study it is demonstrated that women who experienced a hypertensive disorder of pregnancy are at increased risk to develop hypertension later in life and were diagnosed 7.7 years earlier than women who did not experience this complication. In concurrence with results of other studies showing strong relations with cardiovascular events, we found that women with a history of hypertensive disorder of pregnancy are at increased risk to develop ischemic heart disease, stroke and other cardiovascular disease. Based on our data, particularly hypertension seems to be an intermediate in the development of cardiovascular disease in women with hypertensive disorder of pregnancy. In a meta-analysis it is showed that the risk of fatal and non-fatal cardiovascular disease later in life is two-fold in women with a history of spontaneous preterm delivery as compared to women with a term delivery. Moreover, another cohort study in this thesis shows that women with a previous cardiovascular event and a history of early preterm delivery had a substantially higher risk of recurrent cardiovascular mortality compared to women without such an obstetric history. Part 3 of this thesis focuses on clinical implications and presents a Dutch multidisciplinary evidence-based guideline on cardiovascular risk management after reproductive and pregnancy disorders. For pregnancy induced hypertension, small-for-gestational-age infant, recurrent miscarriage, polycystic ovary syndrome and premature ovarian insufficiency a moderate increased relative risk (≤2) was found for the development of cardiovascular disease later in life. Preeclampsia (RR 2.15, 95% CI 1.76-2.61) and spontaneous preterm delivery (RR 2.01, 95% CI 1.52-2.65) were both related to a doubled risk of developing or dying from cardiovascular disease. Only preeclampsia fulfilled the criteria for cardiovascular follow-up. For women who experience preeclampsia in pregnancy it is recommended to assess a full cardiovascular risk profile at the age of 50 years in accordance with the Dutch guideline for cardiovascular risk management.