Inherited High Cholesterol Linked to Modestly Higher Pre-Eclampsia Risk in Observational Study

A study published in the European Journal of Preventive Cardiology reports that women with familial hypercholesterolemia, an inherited condition that causes lifelong high cholesterol, developed pre-eclampsia somewhat more often than other women. Among women with the condition, 11 percent had experienced it. Among a matched comparison group, the figure was 7 percent.

Familial hypercholesterolemia, or FH, raises the risk of heart disease substantially. It affects roughly 1 in 200 to 300 people, though most of them have never been diagnosed. People with high cholesterol carry elevated levels of total cholesterol in the blood, particularly LDL, the so-called bad kind. Earlier research has linked the non-inherited form of high cholesterol to differences in women's reproductive health and pregnancy outcomes. But the picture has been murky, because it is hard to separate the effects of cholesterol itself from those of lifestyle-related factors.

The new work is an observational study led by researchers at Erasmus MC, University Medical Center Rotterdam. It compared 484 women with FH to 968 controls, all aged 40 and over, in the Netherlands and Norway. Recruitment ran from 2023 to 2025. Each woman with FH was matched to two controls on age, smoking status, BMI and ethnicity, and information on reproductive history and pregnancy outcomes was gathered through an online survey.

Pre-eclampsia is defined by high blood pressure in pregnancy together with organ damage. It can slow growth of the baby during pregnancy and lead to premature birth, and in some cases the complications are serious and potentially life-threatening. There is no cure, though treatment and care plans can help women manage symptoms and keep the baby as healthy as possible.

On almost everything else, the two groups looked alike. The researchers found no statistically significant differences in other reproductive health or pregnancy outcomes, and women with FH had a comparable number of pregnancies. Professor Jeanine Roeters van Lennep, a study author, said pre-eclampsia was more common in women with FH but the difference was relatively modest, and she hoped the lack of other differences would reassure these women. The authors also stress that the findings do not mean any individual woman with FH will develop pre-eclampsia.

Because the study is observational, it cannot show cause. Study author Janneke Mulder said the team cannot conclude that FH or high LDL cholesterol causes pre-eclampsia. Still, she said, reproductive health counselling should be considered part of cardiovascular care for women with FH, and possibly for women with high cholesterol more broadly. Women with FH who are planning a pregnancy, she said, should talk with their healthcare team about cardiovascular risk factors, blood pressure and how lipid-lowering treatment should be handled around pregnancy. The team suggests doctors may find it useful to consider pre-eclampsia within cardiovascular risk assessment, especially when a pregnancy is planned.

The researchers note limits. Most women with FH in the study were on lipid-lowering therapy, but likely began it only in their 30s and 40s, when such drugs became widely available. Whether earlier or more intensive treatment could lower pre-eclampsia risk remains unanswered. The participants were predominantly of European ancestry, which restricts how far the results can be generalized to other populations.

The authors place the work in a wider context: reproductive and cardiovascular health are linked. Earlier menstruation or earlier menopause is associated with greater cardiovascular risk, cholesterol shifts across the menstrual cycle and pregnancy, and adverse pregnancy outcomes have been tied to long-term heart risk. Study author Julie van Oortmerssen said the team wants larger longitudinal studies of women with different levels of lifelong LDL exposure, to learn whether high cholesterol combined with complications like pre-eclampsia flags women at particularly high long-term risk who might benefit from closer follow-up or more intensive prevention.