Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 11;31(7):892-900.
doi: 10.1093/eurjpc/zwae028.

Beyond early LDL cholesterol lowering to prevent coronary atherosclerosis in familial hypercholesterolaemia

Shirin Ibrahim  1 , Laurens F Reeskamp  1 , Jim N de Goeij  1 , G Kees Hovingh  1 , R Nils Planken  2 , Willem A Bax  3 , James K Min  4 , James P Earls  4   5 , Paul Knaapen  6 , Albert Wiegman  7 , Erik S G Stroes  1 , Nick S Nurmohamed  1   5   6
Affiliations

Beyond early LDL cholesterol lowering to prevent coronary atherosclerosis in familial hypercholesterolaemia

Shirin Ibrahim et al. Eur J Prev Cardiol. .

Abstract

Aims: Familial hypercholesterolaemia (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 and results: Familial hypercholesterolaemia 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. Ninety genetically diagnosed FH patients and 45 unaffected volunteers (mean age 41 ± 3 years, 51 (38%) female) were included. Familial hypercholesterolaemia 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 per cent 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. Familial hypercholesterolaemia 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.

Conclusion: 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.

Keywords: AI-QCT; CCTA; Coronary plaque burden; Cumulative LDL cholesterol exposure; Familial hypercholesterolaemia.

Plain language summary

This study reveals that young patients with familial hypercholesterolaemia (FH), as compared with individuals without FH, have a higher build-up of coronary artery plaque, linked directly to their increased lifetime exposure to LDL cholesterol. Genetically confirmed FH patients have a higher coronary plaque burden than those without FH, with every 75 mmol/L ∗ years increase in lifetime cumulative LDL cholesterol exposure resulting in a two-fold increase in total plaque volume. Early and potent LDL cholesterol lowering treatments are crucial for FH patients to prevent future cardiovascular diseases.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: L.F.R. is cofounder of Lipid Tools and reports speakers fee from Ultragenyx. G.K.H. reports research grants from the Netherlands Organization for Scientific Research (vidi 016.156.445), CardioVascular Research Initiative, European Union, and the Klinkerpad fonds, institutional research support from Aegerion, Amgen, AstraZeneca, Eli Lilly, Genzyme, Ionis, Kowa, Pfizer, Regeneron, Roche, Sanofi, and The Medicines Company; speaker’s bureau and consulting fees from Amgen, Aegerion, Sanofi, and Regeneron until April 2019 (fees paid to the academic institution); and part-time employment and stock holder of at Novo Nordisk A/S, Denmark since April 2019. W.A.B. reports lecturing fees and advisory board fees from Amgen, Boehringer Ingelheim, Sanofi, Bayer, AstraZeneca, Novartis, and Novo Nordisk. P.K. has received research grants from HeartFlow, Inc. A.W. reports payment or honoraria for participation in safety board for Amryt, in steering committee for Novartis, and research support from Amgen, Regeneron, Novartis, Silence Therapeutics, and Esperion. E.S.G.S. has received ad-board/lecturing fees, paid to the institution, from: Amgen, Sanofi, AstraZeneca, Esperion, Daiichi Sankyo, NovoNordisk, Ionis/Akcea, and Amarin. N.S.N. is cofounder of Lipid Tools. The other authors report no disclosures.

Comment in

Publication types

MeSH terms

Substances