Familial Hypercholesterolemia and Lipoprotein(a): A Gordian Knot in Cardiovascular Prevention
Amalia Despoina Koutsogianni,
Petros Spyridonas Adamidis,
Fotios Barkas,
Evangelos Liberopoulos,
Ta-Chen Su,
Shizuya Yamashita,
George Liamis,
Manfredi Rizzo
Affiliations
Amalia Despoina Koutsogianni
Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
Petros Spyridonas Adamidis
Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
Fotios Barkas
Department of Hygiene and Epidemiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
Evangelos Liberopoulos
1st Propaedeutic Department of Medicine, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, 10679 Athens, Greece
Ta-Chen Su
Departments of Environmental and Occupational Medicine and Internal Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei 10617, Taiwan
Shizuya Yamashita
Department of Cardiology, Rinku General Medical Center, Rinku Ourai Kita 2-23, Osaka 598-8577, Japan
George Liamis
Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
Manfredi Rizzo
Department of Internal Medicine and Medical Specialties, School of Medicine, University of Palermo, 90133 Palermo, Italy
Familial hypercholesterolemia (FH) is the most frequent genetic disorder resulting in increased low-density lipoprotein cholesterol (LDL-C) levels from childhood, leading to premature atherosclerotic cardiovascular disease (ASCVD) if left untreated. FH diagnosis is based on clinical criteria and/or genetic testing and its prevalence is estimated as being up to 1:300,000–400,000 for the homozygous and ~1:200–300 for the heterozygous form. Apart from its late diagnosis, FH is also undertreated, despite the available lipid-lowering therapies. In addition, elevated lipoprotein(a) (Lp(a)) (>50 mg/dL; 120 nmol/L), mostly genetically determined, has been identified as an important cardiovascular risk factor with prevalence rate of ~20% in the general population. Novel Lp(a)-lowering therapies have been recently developed and their cardiovascular efficacy is currently investigated. Although a considerable proportion of FH patients is also diagnosed with high Lp(a) levels, there is a debate whether these two entities are associated. Nevertheless, Lp(a), particularly among patients with FH, has been established as a significant cardiovascular risk factor. In this narrative review, we present up-to-date evidence on the pathophysiology, diagnosis, and treatment of both FH and elevated Lp(a) with a special focus on their association and joint effect on ASCVD risk.
