Beyond Early LDL Cholesterol Lowering to Prevent Coronary Atherosclerosis in Familial Hypercholesterolemia

Authors

Shirin Ibrahim, Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Laurens F. Reeskamp, Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Jim N. de Goeij, Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
G Kees Hovingh, Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
R Nils Planken, Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Willem A. Bax, Department of Internal Medicine, Northwest Clinics, Alkmaar, the Netherlands.
James K. Min, Cleerly Inc., Denver, CO, United States.
James P. Earls, Cleerly Inc., Denver, CO, United States.
Paul Knaapen, Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Albert Wiegman, Department of Paediatrics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Erik S. Stroes, Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Nick S. Nurmohamed, Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Document Type

Journal Article

Publication Date

1-19-2024

Journal

European journal of preventive cardiology

DOI

10.1093/eurjpc/zwae028

Keywords

AI-QCT; CCTA; Familial hypercholesterolemia; coronary plaque burden; cumulative LDL cholesterol exposure

Abstract

BACKGROUND: Familial hypercholesterolemia (FH) patients are subjected to a high lifetime exposure to low-density lipoprotein cholesterol (LDL-C), despite use of lipid-lowering therapy (LLT). This study aimed to quantify the extent of subclinical atherosclerosis and to evaluate the association between lifetime cumulative LDL-C exposure and coronary atherosclerosis in young FH patients. METHODS: FH patients, divided into a subgroup of early treated (LLT initiated <25 years) and late treated (LLT initiated ≥25 years) patients, and an age- and sex-matched unaffected control group, underwent coronary CT angiography (CCTA) with artificial intelligence-guided analysis. RESULTS: Ninety genetically diagnosed FH patients and 45 unaffected volunteers (mean age 41 ± 3 years, 51 (38%) female) were included. FH patients had higher cumulative LDL-C exposure (181 ± 54 vs. 105 ± 33 mmol/l*years) and higher prevalence of coronary plaque compared with controls (46 [51%] vs. 10 [22%], OR 3.66 [95%CI 1.62-8.27]). Every 75 mmol/l*years cumulative exposure to LDL-C was associated with a doubling in percent atheroma volume (total plaque volume divided by total vessel volume). Early treated patients had a modestly lower cumulative LDL-C exposure compared with late treated FH patients (167 ± 41 vs. 194 ± 61 mmol/l*years; p = 0.045), without significant difference in coronary atherosclerosis. FH patients with above-median cumulative LDL-C exposure had significantly higher plaque prevalence (OR 3.62 [95%CI 1.62-8.27]; p = 0.001), compared with patients with below-median exposure. CONCLUSIONS: Lifetime exposure to LDL-C determines coronary plaque burden in FH, underlining the need of early as well as potent treatment initiation. Periodic CCTA may offer a unique opportunity to monitor coronary atherosclerosis and personalize treatment in FH.

APA Citation

Ibrahim, Shirin; Reeskamp, Laurens F.; de Goeij, Jim N.; Hovingh, G Kees; Planken, R Nils; Bax, Willem A.; Min, James K.; Earls, James P.; Knaapen, Paul; Wiegman, Albert; Stroes, Erik S.; and Nurmohamed, Nick S., "Beyond Early LDL Cholesterol Lowering to Prevent Coronary Atherosclerosis in Familial Hypercholesterolemia" (2024). GW Authored Works. Paper 4152.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4152

Department

Radiology