Extreme LDL-C concentration is associated with increased cardiovascular disease in women with homozygous familial hypercholesterolemia

Martine Paquette; Isabelle Ruel; Simon-Pierre Guay; Zobaida Al-Baldawi; Diane Brisson; Daniel Gaudet; Patrick Couture; Jean Bergeron; Robert A Hegele; Gordon A Francis; Mark H Sherman; Ruth McPherson; Thomas Ransom; Liam R Brunham; Gb John Mancini; Brian W McCrindle; Iulia Iatan; Jacques Genest; Alexis Baass

doi:10.1016/j.jacl.2024.10.008

Extreme LDL-C concentration is associated with increased cardiovascular disease in women with homozygous familial hypercholesterolemia

J Clin Lipidol. 2024 Nov 6:S1933-2874(24)00269-1. doi: 10.1016/j.jacl.2024.10.008. Online ahead of print.

Authors

Martine Paquette¹, Isabelle Ruel², Simon-Pierre Guay³, Zobaida Al-Baldawi⁴, Diane Brisson⁵, Daniel Gaudet⁵, Patrick Couture⁶, Jean Bergeron⁶, Robert A Hegele⁷, Gordon A Francis⁸, Mark H Sherman⁹, Ruth McPherson¹⁰, Thomas Ransom¹¹, Liam R Brunham⁸, Gb John Mancini¹², Brian W McCrindle¹³, Iulia Iatan², Jacques Genest², Alexis Baass¹⁴

Affiliations

¹ Lipids, Nutrition, and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal, Québec, Canada.
² Research Institute of the McGill University Health Centre, Montreal, Québec, Canada.
³ Lipids, Nutrition, and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal, Québec, Canada; Department of Medicine, Division of Endocrinology, Université de Montréal, Montréal, Québec, Canada.
⁴ Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁵ ECOGENE-21 Clinical and Translational Research Center, Chicoutimi, Québec, Canada.
⁶ Lipid clinic, Department of Specialized Medicine, CHU de Québec - Université Laval, Québec City, Québec, Canada.
⁷ Departments of Medicine and Biochemistry, Schulich School of Medicine and Robarts Research Institute, Western University, London, Ontario, Canada.
⁸ Centre for Heart Lung Innovation, Providence Health Care Research Institute; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
⁹ Department of Endocrinology, McGill University Health Centre, Montreal, Québec, Canada.
¹⁰ Lipid Clinic & Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
¹¹ Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, New Scotland, Canada.
¹² Centre for Cardiovascular Innovation, University of British Columbia, Vancouver, BC, Canada.
¹³ Department of Pediatrics, The Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
¹⁴ Lipids, Nutrition, and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal, Québec, Canada; Department of Medicine, Divisions of Experimental Medicine and Medical Biochemistry, McGill University, Montreal, Québec H3G 2M1, Canada. Electronic address: alexis.baass@ircm.qc.ca.

PMID: 39638644
DOI: 10.1016/j.jacl.2024.10.008

Abstract

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease of low-density lipoprotein cholesterol (LDL-C) metabolism. Despite the devastating effect of this disease on atherosclerotic cardiovascular health, the disease phenotype and severity are more heterogeneous than previously thought. The predictors of atherosclerotic cardiovascular disease (ASCVD) in HoFH patients have never been systematically studied.

Objective: To investigate the univariate and multivariate predictors of ASCVD in HoFH patients.

Methods: Patients from the Canadian HoFH Registry were included in the present retrospective longitudinal study. Data for these patients were collected using a standardized questionnaire between 2019 and 2022 in 19 academic sites across Canada. Predictors of ASCVD were evaluated using Cox proportional hazards models.

Results: Among 48 HoFH patients, 26 (54 %) of them had at least one ASCVD event. The average age at baseline was 19 ± 15 years and women represented 56 % of the cohort. The independent predictors of ASCVD events were male sex (HR 2.57 (1.13-5.84)), diabetes (HR 16.22 (3.38-77.97)), and LDL-C above the median of 14.45 mmol/L [559 mg/dL] (HR 3.10 (1.24-7.76)). When performing subgroup analysis according to sex, the presence of LDL-C above median was associated with a significantly higher probability of ASCVD (88 % vs. 43 %, p = 0.005) in women, but not in men (100 % at age 40 in both groups, p = 0.98).

Conclusion: This study reported for the first time the univariate and multivariate predictors of ASCVD in HoFH patients. We demonstrate that predictors of ASCVD in HoFH differ in males and females with respect to LDL-C levels.

Keywords: Cardiovascular; Familial hypercholesterolemia; Homozygous; LDL-C; Risk factors.