Estimated Small Dense LDL Cholesterol and Coronary Artery Disease in Familial Hypercholesterolemia
Abstract
AIM: Recent evidence reports good agreement between measured and estimated small-dense low-density lipoprotein cholesterol (EsdLDL-C) using a readily applicable formula. Its clinical utility in heterozygous familial hypercholesterolemia (HeFH) has not yet been evaluated. We aimed to evaluate the sex-specific associations of pre-treatment EsdLDL-C with coronary artery disease (CAD) prevalence in adult patients with HeFH and its discriminative value beyond LDL-C. METHODS: Data from consecutively recruited adults with a clinical diagnosis of HeFH from an ongoing registry (HELLAS-FH, n = 3,276) were analyzed. Patient demographics, lipid parameters, CAD risk factors, and CAD prevalence at registry enrollment were evaluated. EsdLDL-C was calculated at pre-treatment (i.e., before any hypolipidemic therapy initiation) using the Sampson equation. RESULTS: EsdLDL-C was associated with an increased prevalence of type 2 diabetes and hypertension, a higher body mass index and triglycerides, and lower high-density lipoprotein cholesterol. EsdLDL-C was also the strongest independent lipid-associated factor for CAD (OR: 1.24, p＜0.001). This association was more pronounced in women (OR 1.57, p＜0.001). EsdLDL-C showed higher CAD discrimination than LDL-C (AUC 0.611 vs. 0.522). Incorporating EsdLDL-C into the best discriminative model improved discriminative ability vs the core model (AUC 0.831 vs 0.828, p = 0.038) and overall model fit (ΔAIC) = -10.3). This incremental predictive value was driven predominantly by females (ΔAIC = -14.1; AUC 0.787 vs 0.769, p = 0.015). CONCLUSION: In a large sample of patients with clinical HeFH, EsdLDL-C was incrementally associated with CAD beyond LDL-C. This finding was more pronounced in women. The clinical utility of this readily available lipid marker as a risk enhancer should therefore be further investigated.
Related
- Effect of rosuvastatin and ezetimibe therapy on LDL-cholesterol reduction and non-invasive arterial injury markers in children with heterozygous familial hypercholesterolemia: a prospective, open-label, randomized study
- Reclassification of Clinical Familial Hypercholesterolemia Diagnoses After Adjustment of LDL-C for Lipoprotein(a) Cholesterol: A Systematic Review and Meta-Analysis
- Expectations for Angiopoietin-like 3 Inhibitors Taking Broad Lipid-modifying Effects on the Comprehensive Control of Atherosclerotic Cardiovascular Disease Risk in Patients with Homozygous Familial Hypercholesterolemia
- Familial Hypercholesterolemia Screening: From Pediatric Detection to Life-long Management
- Association between LDL-cholesterol, statin therapy, physical activity and inflammatory markers in patients with stable coronary heart disease
BibTeX
@article{delialis2026estimated,
title = {{Estimated Small Dense LDL Cholesterol and Coronary Artery Disease in Familial Hypercholesterolemia}},
author = {Dimitrios Delialis and Christos V. Rizos and Evmorfia Aivalioti and Chrysoula Moustou and George Liamis and Ioannis Skoumas and George Sfikas and Genovefa Kolovou and Loukianos Rallidis and Anastasia Garoufi and Konstantinos Tziomalos and Emmanouil Skalidis and Vasileios Kotsis and Evgenia Mavrokefalou and Michalis Doumas and Vaia Lambadiari and Panagiotis Anagnostis and Theodosios Filippatos and Amalia Boufidou and Vasiliki Giannakopoulou and Georgia Anastasiou and Spyridon Spantidakis and Charalambos Vlachopoulos and Ioanna Dima and Charalambos Koumaras and Elisavet Prodromiadou and Vana Kolovou and Georgios Fakas and Konstantinos A. Papathanasiou and Achilleas Attilakos and Dimitrios Agapakis and Evangelos Zacharis and Christina Antza and Aspasia Antonopoulou and Chrysoula Boutari and Aikaterini Kountouri and Maria Pappa and Evangelia Koukou and Eleni Mpellou and Evangelos Liberopoulos and Kimon Stamatelopoulos},
journal = {Journal of Atherosclerosis and Thrombosis},
year = {2026},
month = oct,
doi = {10.5551/jat.66409},
url = {https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66409/_article},
note = {CC BY-NC-SA},
}
RIS
TY - JOUR
TI - Estimated Small Dense LDL Cholesterol and Coronary Artery Disease in Familial Hypercholesterolemia
AU - Dimitrios Delialis
AU - Christos V. Rizos
AU - Evmorfia Aivalioti
AU - Chrysoula Moustou
AU - George Liamis
AU - Ioannis Skoumas
AU - George Sfikas
AU - Genovefa Kolovou
AU - Loukianos Rallidis
AU - Anastasia Garoufi
AU - Konstantinos Tziomalos
AU - Emmanouil Skalidis
AU - Vasileios Kotsis
AU - Evgenia Mavrokefalou
AU - Michalis Doumas
AU - Vaia Lambadiari
AU - Panagiotis Anagnostis
AU - Theodosios Filippatos
AU - Amalia Boufidou
AU - Vasiliki Giannakopoulou
AU - Georgia Anastasiou
AU - Spyridon Spantidakis
AU - Charalambos Vlachopoulos
AU - Ioanna Dima
AU - Charalambos Koumaras
AU - Elisavet Prodromiadou
AU - Vana Kolovou
AU - Georgios Fakas
AU - Konstantinos A. Papathanasiou
AU - Achilleas Attilakos
AU - Dimitrios Agapakis
AU - Evangelos Zacharis
AU - Christina Antza
AU - Aspasia Antonopoulou
AU - Chrysoula Boutari
AU - Aikaterini Kountouri
AU - Maria Pappa
AU - Evangelia Koukou
AU - Eleni Mpellou
AU - Evangelos Liberopoulos
AU - Kimon Stamatelopoulos
PY - 2026
DA - 2026/10/24
JO - Journal of Atherosclerosis and Thrombosis
DO - 10.5551/jat.66409
UR - https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66409/_article
AB - AIM: Recent evidence reports good agreement between measured and estimated small-dense low-density lipoprotein cholesterol (EsdLDL-C) using a readily applicable formula. Its clinical utility in heterozygous familial hypercholesterolemia (HeFH) has not yet been evaluated. We aimed to evaluate the sex-specific associations of pre-treatment EsdLDL-C with coronary artery disease (CAD) prevalence in adult patients with HeFH and its discriminative value beyond LDL-C. METHODS: Data from consecutively recruited adults with a clinical diagnosis of HeFH from an ongoing registry (HELLAS-FH, n = 3,276) were analyzed. Patient demographics, lipid parameters, CAD risk factors, and CAD prevalence at registry enrollment were evaluated. EsdLDL-C was calculated at pre-treatment (i.e., before any hypolipidemic therapy initiation) using the Sampson equation. RESULTS: EsdLDL-C was associated with an increased prevalence of type 2 diabetes and hypertension, a higher body mass index and triglycerides, and lower high-density lipoprotein cholesterol. EsdLDL-C was also the strongest independent lipid-associated factor for CAD (OR: 1.24, p＜0.001). This association was more pronounced in women (OR 1.57, p＜0.001). EsdLDL-C showed higher CAD discrimination than LDL-C (AUC 0.611 vs. 0.522). Incorporating EsdLDL-C into the best discriminative model improved discriminative ability vs the core model (AUC 0.831 vs 0.828, p = 0.038) and overall model fit (ΔAIC) = -10.3). This incremental predictive value was driven predominantly by females (ΔAIC = -14.1; AUC 0.787 vs 0.769, p = 0.015). CONCLUSION: In a large sample of patients with clinical HeFH, EsdLDL-C was incrementally associated with CAD beyond LDL-C. This finding was more pronounced in women. The clinical utility of this readily available lipid marker as a risk enhancer should therefore be further investigated.
SN - 1880-3873
SN - 1340-3478
ER -