Young women with familial hypercholesterolemia have higher LDL-cholesterol burden than men: Novel data using repeated measurements during 12-years follow-up

Anja K Johansen; Martin P Bogsrud; Jacob J Christensen; Amanda Rundblad; Ingunn Narverud; Stine Ulven; Gisle Langslet; Kjetil Retterstøl; Kirsten B Holven

doi:10.1016/j.athplu.2023.01.001

Young women with familial hypercholesterolemia have higher LDL-cholesterol burden than men: Novel data using repeated measurements during 12-years follow-up

Atheroscler Plus. 2023 Mar 2:51:28-34. doi: 10.1016/j.athplu.2023.01.001. eCollection 2023 Mar.

Authors

Anja K Johansen^{1

2}, Martin P Bogsrud³, Jacob J Christensen², Amanda Rundblad², Ingunn Narverud^{1

2}, Stine Ulven², Gisle Langslet⁴, Kjetil Retterstøl^{2

4}, Kirsten B Holven^{1

2}

Affiliations

¹ Norwegian National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital, Oslo, Norway.
² Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
³ Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital, Oslo, Norway.
⁴ Lipid Clinic, Oslo University Hospital, Oslo, Norway.

Abstract

Background and aims: The concentration and the duration of exposure to low-density lipoprotein cholesterol (LDL-C) (LDL-C burden) is an important determinant of risk for cardiovascular disease and thresholds has recently been estimated. Individuals with familial hypercholesterolemia (FH) have increased risk of premature cardiovascular disease. The overall aim of the present study was to describe differences in LDL-C level and LDL-C burden in females and males with FH visiting an outpatient lipid clinic from a young age, using multiple LDL-C measurements during a follow-up time of 12 years. First, we aimed to study if the LDL-C concentration and the LDL-C burden is different between females and males at ages 0-10, 10-20, 20-30 and >30 years. Second, we aimed to estimate the subject-specific LDL-C burden at age 19 and 30 years, and the proportion of female and male patients that reach suggested LDL-C thresholds indicating high risk of ASCVD.

Methods: Data was retrospectively collected from medical records of 438 subjects (207 girls and 231 boys) with FH, referred to the Lipid Clinic, Oslo University Hospital below the age of 19 years. The LDL-C burden was estimated based on repeated LDL-C measurements over time.

Results: Subjects were followed over a period of mean 12.0 (SD 7.0) years, with median 10 years (7-17; 25-75 percentiles, minimum 2), with median 6 (4-9; 25-75 percentiles, minimum 2) available LDL-C measurements, starting at mean age 11 (SD 3.9) years. There was a difference in both LDL-C and LDL-C burden between sexes at different ages. On average, males had lower LDL-C over time, although this difference was less pronounced with age and males also had lower estimated LDL-C burden over time, and this difference was further exacerbated with age.

Conclusion: Our study shows that young women with FH have a higher LDL-C burden than their male counterparts, potentially explaining the increased excess CVD risk seen among these. It underscores the importance of careful-follow up and early treatment initiation both prior to and after pregnancies in order to limit statin-free periods.

Keywords: Cholesterol lowering; Familial hypercholesterolemia; Low-density-lipoprotein exposure; Sex-differences.