Purpose of Review
Familial hypercholesterolemia (FH) is the most common genetic metabolic disorder characterized by markedly elevated LDL-C levels from birth leading to atherosclerotic cardiovascular disease (ASCVD) and premature deaths. The purpose of this review is to share the current knowledge in the diagnosis, risk estimation, and management of patients with FH in the light of recent evidence and guideline recommendations.
Recent registries underscored the prevalence of FH as 1/200–250 translating to an almost 1500 million subjects suffering from FH worldwide. However, only a minority of FH patients are identified early and effectively treated. In most cases, mutations in the LDL-receptor (LDLR) gene and to a lesser degree in the apolipoprotein B-100 (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL-receptor adaptor protein 1 (LDLRAP1) genes cause FH. Diagnostic scores such as Dutch Lipid Clinic Network criteria using clinical manifestations are helpful in identifying FH. Traditional risk factors and high lipoprotein(a) affect the course of the disease. Vascular ultrasound imaging and coronary calcium scoring are helpful for further risk estimation of these patients. Getting to LDL-C goals is possible with currently available treatments including statins, ezetimibe, and PCSK9 inhibitors, as well as lipoprotein apheresis, lomitapide, and mipomersen in more severe phenotypes. Additionally, novel agents bempedoic acid, inclisiran, and evinacumab expanded the treatment choices for some patients with FH. Early diagnosis and initiation of LDL-C lowering are still required to achieve the greatest reduction in ASCVD morbidity and mortality in patients with FH.
FH is a common genetic disorder characterized by markedly elevated LDL-C levels from birth onward, resulting in significantly increased risk for ASCVD. Despite major advances in our understanding of the disease and effective therapies, FH is still underdiagnosed and undertreated. Early initiation of LDL-C lowering by increased awareness of FH among the healthcare professionals, patients, and the public is necessary to achieve meaningful reduction in ASCVD morbidity and mortality in these patients.