Obesity and atherosclerotic cardiovascular disease in adults with heterozygous familial hypercholesterolemia: An analysis from HELLAS-FH registry

Fotios Barkas; Christos V Rizos; George Liamis; Ioannis Skoumas; Anastasia Garoufi; Loukianos Rallidis; Genovefa Kolovou; Konstantinos Tziomalos; Emmanouil Skalidis; George Sfikas; Vasilios Kotsis; Michalis Doumas; Panagiotis Anagnostis; Vaia Lambadiari; Georgia Anastasiou; Iosif Koutagiar; Achilleas Attilakos; Estela Kiouri; Vana Kolovou; Georgios Polychronopoulos; Amalia-Despoina Koutsogianni; Evangelos Zacharis; Charalambos Koumaras; Christina Antza; Chrysoula Boutari; Evangelos Liberopoulos

doi:10.1016/j.jacl.2024.01.005

Obesity and atherosclerotic cardiovascular disease in adults with heterozygous familial hypercholesterolemia: An analysis from HELLAS-FH registry

J Clin Lipidol. 2024 Jan 24:S1933-2874(24)00005-9. doi: 10.1016/j.jacl.2024.01.005. Online ahead of print.

Authors

Fotios Barkas¹, Christos V Rizos², George Liamis², Ioannis Skoumas³, Anastasia Garoufi⁴, Loukianos Rallidis⁵, Genovefa Kolovou⁶, Konstantinos Tziomalos⁷, Emmanouil Skalidis⁸, George Sfikas⁹, Vasilios Kotsis¹⁰, Michalis Doumas¹¹, Panagiotis Anagnostis¹², Vaia Lambadiari¹³, Georgia Anastasiou², Iosif Koutagiar³, Achilleas Attilakos¹⁴, Estela Kiouri⁵, Vana Kolovou⁶, Georgios Polychronopoulos⁷, Amalia-Despoina Koutsogianni², Evangelos Zacharis⁸, Charalambos Koumaras⁹, Christina Antza¹⁰, Chrysoula Boutari¹¹, Evangelos Liberopoulos¹⁵

Affiliations

¹ Department of Hygiene & Epidemiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece (Dr Barkas); Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece (Drs Rizos, Liamis, Anastasiou, Zacharis).
² Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece (Drs Rizos, Liamis, Anastasiou, Zacharis).
³ Cardiology Clinic, Hippokration General Hospital, Athens, Greece (Drs Skoumas and Koutagiar).
⁴ 2nd Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, "P. & A. Kyriakou" Children's Hospital, Athens, Greece (Dr Garoufi).
⁵ Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Attikon University General Hospital, Athens, Greece (Drs Rallidis and Kiouri).
⁶ Cardiometabolic Centre, Lipid Clinic, LA apheresis Unit, Metropolitan Hospital, Athens, Greece (Dr Kolovou).
⁷ 1st Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece (Drs Tziomalos and Polychronopoulos).
⁸ Cardiology Clinic, University General Hospital of Heraklion, Heraklion, Greece (Drs Skalidis and Zacharis).
⁹ Department of Internal Medicine, 424 General Military Training Hospital, Thessaloniki, Greece (Drs Sfikas and Koumaras).
¹⁰ Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Papageorgiou General Hospital Thessaloniki, Thessaloniki, Greece (Drs Kotsis and Antza).
¹¹ Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki, Greece (Drs Doumas and Boutari).
¹² Department of Endocrinology, Police Medical Centre, Thessaloniki, Greece (Dr Anagnostis).
¹³ 2nd Propaedeutic Internal Medicine Department and Diabetes Research Unit, National and Kapodistrian University of Athens, Attikon University General Hospital, Athens, Greece (Dr Lambadiari).
¹⁴ Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, C' Pediatrics Clinic, Attikon University General Hospital, Athens, Greece (Dr Attilakos).
¹⁵ 1st Propedeutic Department of Medicine, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital of Athens, Athens, Greece (Dr Liberopoulos). Electronic address: elibero@med.uoa.gr.

PMID: 38331687
DOI: 10.1016/j.jacl.2024.01.005

Abstract

Background: Familial hypercholesterolemia (FH) and obesity are well-established risk factors of atherosclerotic cardiovascular disease (ASCVD). Despite high prevalence, their joint association with ASCVD remains largely unknown.

Objective: To investigate the association of obesity with prevalent ASCVD in individuals with heterozygous FH (HeFH) enrolled in the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH).

Methods: FH diagnosis was based on Dutch Lipid Clinic Network (DLCN) criteria. Adults with at least possible FH diagnosis (DLCN score ≥3) and available body mass index (BMI) values were included. Homozygous FH individuals were excluded.

Results: 1655 HeFH adults (mean age 51.0 ± 14.4 years, 48.6% female) were included; 378 (22.8%) and 430 (26.0%) were diagnosed with probable and definite FH, respectively. Furthermore, 371 participants (22.4%) had obesity and 761 (46.0%) were overweight. Prevalence of ASCVD risk factors increased progressively with BMI. Prevalence of coronary artery disease (CAD) was 23.4% (3.2% for stroke and 2.7% for peripheral artery disease, PAD), and increased progressively across BMI groups. After adjusting for traditional ASCVD risk factors and lipid-lowering medication, individuals with obesity had higher odds of established CAD (OR: 1.54, 95% CI: 1.04-2.27, p = 0.036) as well as premature CAD (OR: 1.74, 95% CI: 1.17-2.60, p = 0.009) compared with those with normal BMI. No association was found with stroke or PAD.

Conclusions: Over half of adults with HeFH have overweight or obesity. Obesity was independently associated with increased prevalence of CAD in this population.

Keywords: Atherosclerotic cardiovascular disease; Body mass index; Familial hypercholesterolemia; Obesity; Overweight.