Women with familial hypercholesterolemia face a higher cardiovascular risk
Familial hypercholesterolemia presents unique challenges for women throughout their lives, increasing their risk of cardiovascular diseases. From birth, girls with this genetic condition have higher LDL cholesterol levels than boys, and this difference widens with age. By the age of 19, women have already accumulated a significantly higher LDL cholesterol burden than men, making them more susceptible to complications such as atherosclerosis.
Diagnosis in women often occurs later, with a delay of 3 to 7 years compared to men. This situation prolongs their exposure to high LDL cholesterol levels, a key factor in the development of heart disease. Additionally, treatments to lower cholesterol are less frequently prescribed to women, who also have a 37% lower chance of achieving recommended therapeutic targets.
The childbearing period is a particularly vulnerable phase. Lipid-lowering treatments are typically discontinued before pregnancy, during pregnancy, and while breastfeeding, resulting in an average loss of 2.3 years of statin treatment per woman. Some may even go without treatment for up to 14 years, equivalent to a 20% reduction in the protective years provided by statins over a lifetime. During pregnancy, LDL cholesterol levels naturally increase by 30 to 50%, but in women with familial hypercholesterolemia, they can reach extreme levels, sometimes exceeding 8 or 9 mmol/L. This rise, combined with the discontinuation of medication, exposes women to prolonged periods of uncontrolled cholesterol levels.
Menopause marks another critical stage. LDL cholesterol levels increase by an average of 12% during this transition, with an even more pronounced rise in women carrying the mutation responsible for familial hypercholesterolemia. After the age of 50, their LDL cholesterol levels become, on average, 0.6 mmol/L higher than those of men, further accelerating the risk of cardiovascular diseases.
Despite these challenges, women with this condition develop coronary heart disease less often than men, although their relative risk compared to the general female population remains higher. For example, their risk of coronary mortality exceeds that of affected men by 50% compared to the general population. This is explained by their greater cumulative exposure to LDL cholesterol, due to late diagnosis, less intensive treatments, and therapeutic interruptions during the reproductive years.
Available treatments, such as statins, ezetimibe, or PCSK9 inhibitors, can significantly reduce LDL cholesterol. However, women are less likely to receive these treatments or combinations of medications. During pregnancy, options are limited to lipoprotein apheresis or bile acid sequestrants, which are less accessible or less effective. Although statins are generally discouraged during pregnancy, recent studies suggest they could be considered after the first trimester for women at very high risk, subject to a shared decision with the doctor.
Traditional risk factors, such as obesity, type 2 diabetes, hypertension, or smoking, further worsen this picture. Hypertension, in particular, increases the risk of early cardiovascular diseases more in women than in men. However, women remain less likely to develop type 2 diabetes, even though obesity multiplies this risk by five.
In summary, women with familial hypercholesterolemia bear a heavier burden due to biological particularities, diagnostic delays, and less tailored treatments. Their cardiovascular risk, while lower in absolute terms than that of men, remains disproportionate compared to the general female population.
About Our Sources
Original Publication
DOI: https://doi.org/10.1007/s11883-026-01431-1
Title: Familial Hypercholesterolemia in Women: Diagnosis, Treatment, and Cardiovascular Outcomes Across the Lifespan
Journal: Current Atherosclerosis Reports
Publisher: Springer Science and Business Media LLC
Authors: Irene Karungi; Kirsten B. Holven; Kausik K. Ray; Amany Elshorbagy