Risk for Cardiovascular Disease in Pregnant Women with Familial Hypercholesterolemia: A Review on the Endothelial and Hemostatic Balance in a Clinical Perspective

Introduction

Normal pregnancy leads to several alterations in hemostatic parameters. The plasma concentrations of a number of coagulation factors increase, coagulation inhibitors decrease, and fibrinolytic activity is reduced.1 Moreover, a gradual increase in maternal plasma lipid concentrations may also increase cardiovascular risk. In a previous study we followed 22 women with familial hypercholesterolemia (FH) through pregnancy and observed a 30% increase in low density lipoprotein (LDL)-cholesterol (range 6.7 to 8.6 mmol/L) and a 116% increase in fasting triglycerides (range 1.5 to 3.0 mmol/L) from gestational week 17–20 compared to gestational week 36.2 The increase in plasma LDL-cholesterol was higher in FH women than in pregnant controls (1.9 mmol/L vs 0.8 mmol/L) (2). There is a close interaction between plasma lipids and several mediators in the coagulation cascade.3 Further, elevated LDL-cholesterol can lead to the formation of foam cells in the endothelium. Any atherosclerotic plaque may trigger coagulation and pregnancy-associated thromboembolism in veins or arteries is a cause of significant maternal morbidity.4 Since women with familial hypercholesterolemia (FH) are more prone to atherosclerosis than healthy women, they may be particularly vulnerable to alterations in hemostatic parameters during the pregnancy and some case reports have indeed suggested this.5–7 From experience during many years in our Lipid Clinic, we have learned that many women with FH are concerned about the cardiovascular risk in pregnancy. Lack of data have made evidence-based answers difficult to provide. Pregnancy usually will result in a two- to threefold increase in LDL-cholesterol in FH women, since they need to stop taking lipid lowering medications. There are many difficult considerations in the treatment of pregnant women with FH and a possible accelerating atherosclerosis in the mother must be weighed against the very important concern for fetal safety. The UK National Institute for Health and Clinical Excellence (NICE) advice is that women with FH who are considering pregnancy should be provided expertise in both cardiology and obstetrics.8 Clearly, the special challenges associated with pregnancy in women with FH makes it relevant to review the literature in this area, especially in a clinical perspective. The specific issues related to the very rare homozygote FH will not be discussed in the present paper.

Abstract

OBJECTIVES

Familial hypercholesterolemia leads to a markedly increased risk for atherosclerotic disease with a more pronounced increase in relative risk in young middle aged patients versus older. Women with FH need to stop treatment with virtually all types of lipid lowering medication during pregnancy and lactation. The aim of the study was to review the literature to examine if pregnancy increases the risk for vascular disease in women with FH.

METHODS

A search in PubMed for “acute myocardial infarction AND pregnancy” resulted in 433 references on which the present paper is based. These studies were interpreted based on nearly 20 years of clinical experience with the treatment of FH in a large lipid clinic.

RESULTS

Pregnancy increases vascular stress, alters the hemostatic balance, and activates the endothelium, but there is almost no data on clinical vascular disease regarding pregnant women with FH.

CONCLUSION

Several important risk factors for arterial vascular disease are negatively influenced by pregnancy, but current literature is too sparse to allow any conclusion on the risk for major cardiovascular outcomes in women with FH during pregnancy.

Keywords

familial hypercholesterolemia, myocardial infarction, cholesterol, statins, pregnancy