Sex differences in the presentation, treatment and outcomes of patients with homozygous familial hypercholesterolemia

Zobaida Al-Baldawi; Leslie Brown; Isabelle Ruel; Alexis Baass; Jean Bergeron; Lubomira Cermakova; Patrick Couture; Daniel Gaudet; Gordon A Francis; Robert A Hegele; Iulia Iatan; G B John Mancini; Brian W McCrindle; Thomas Ransom; Mark H Sherman; Ruth McPherson; Jacques Genest; Liam R Brunham

doi:10.1016/j.jacl.2024.01.003

Sex differences in the presentation, treatment and outcomes of patients with homozygous familial hypercholesterolemia

J Clin Lipidol. 2024 Mar-Apr;18(2):e189-e196. doi: 10.1016/j.jacl.2024.01.003. Epub 2024 Jan 14.

Authors

Zobaida Al-Baldawi¹, Leslie Brown², Isabelle Ruel², Alexis Baass², Jean Bergeron³, Lubomira Cermakova⁴, Patrick Couture³, Daniel Gaudet⁵, Gordon A Francis⁴, Robert A Hegele⁶, Iulia Iatan⁴, G B John Mancini⁷, Brian W McCrindle⁸, Thomas Ransom⁹, Mark H Sherman¹⁰, Ruth McPherson¹¹, Jacques Genest², Liam R Brunham⁴

Affiliations

¹ Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada (Dr Al-Baldawi).
² Research Institute of the McGill University Health Centre, Montreal, QC, Canada (Drs Brown, Ruel, Baass, Sherman, Genest).
³ Endocrinology and Nephrology Unit, CHU de Québec - Université Laval Research Center, Québec City, QC, Canada (Drs Bergeron, Couture).
⁴ Centre for Heart Lung Innovation, Providence Health Care Research, Institute, Department of Medicine, University of British Columbia, Vancouver, BC, Canada (Drs Cermakova, Francis, Iatan, Brunham).
⁵ ECOGENE-21 Clinical and Translational Research Center, Chicoutimi, QC, Canada (Dr Gaudet).
⁶ Departments of Medicine and Biochemistry, Schulich School of, Medicine and Robarts Research Institute, Western University, London, ON, Canada (Dr Hegele).
⁷ Centre for, Cardiovascular Innovation, University of British Columbia, Vancouver, BC, Canada (Dr Mancini).
⁸ Department of Pediatrics, The Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada (Dr McCrindle).
⁹ Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS, Canada (Dr Ransom).
¹⁰ Research Institute of the McGill University Health Centre, Montreal, QC, Canada (Drs Brown, Ruel, Baass, Sherman, Genest); Department of Endocrinology, McGill University, Health Centre, Montreal, QC, Canada (Dr Sherman).
¹¹ Lipid Clinic & Atherogenomics Laboratory, University, of Ottawa Heart Institute, Ottawa, ON, Canada (Dr McPherson).

PMID: 38281851
DOI: 10.1016/j.jacl.2024.01.003

Abstract

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare, autosomal semi-dominant lipid metabolism disorder characterized by extremely high low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease. The objective of this study was to investigate sex-differences in the treatment and outcomes of patients with HoFH.

Methods: We examined clinical characteristics, lipid-lowering therapy (LLT), and cardiovascular events using descriptive statistics of patients in the Canadian HoFH registry. Major adverse cardiovascular events (MACE) were defined as the composite of cardiovascular death, non-fatal myocardial infarction, and stroke. Sex differences between continuous and categorical variables were analyzed using Mann-Whitney U test and Fisher's Exact test, respectively.

Results: This study included 48 patients (27 (56%) female). The median age at diagnosis in females was 14.0 (interquartile range (IQR) 9.0-30.0) and in males was 8.0 (IQR 2.0-23.0) (p = 0.07). Baseline clinical characteristics were comparable between both sexes. The median baseline LDL-C was 12.7 mmol/L (10.0-18.3) in females and 15.3 (10.5-20.0) in males (p = 0.51). Follow up LDL-C levels were 7.6 mmol/L (IQR 4.8-11.0) in females and 6.3 (IQR 4.6-7.5) in males (p = 0.1). Most patients were taking 3 or more LLTs, with comparable proportions in both sexes (p = 0.26). Apheresis was similar in both sexes, 14 (51.8%) vs. 10 (47.6%) (p = 0.2). Over a mean of 10 years of follow-up, MACE occurred in 3 females (11.1%) and 4 males (19.1%) (p = 0.2).

Conclusion: Lipid levels and treatment were similar between sexes. MACE occurred in similar proportions between sexes, indicating that HoFH offsets the inherently lower cardiovascular risk in pre-menopausal females. Further investigation into sex-differences in HoFH in larger sample sizes is warranted.

Keywords: Cardiovascular outcomes; Homozygous familial hypercholesterolemia; Lipid lowering therapies; Registry-based studies; Sex differences.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Child
Cholesterol, LDL / blood
Female
Homozygote
Humans
Hyperlipoproteinemia Type II / blood
Hyperlipoproteinemia Type II / diagnosis
Hyperlipoproteinemia Type II / drug therapy
Hyperlipoproteinemia Type II / therapy
Male
Sex Characteristics*
Sex Factors
Treatment Outcome
Young Adult

Substances

Cholesterol, LDL