Familial Hypercholesterolemia and Its Current Diagnostics and Treatment Possibilities: A Literature Analysis

Abstract

Familial hypercholesterolemia (FH) is a common, inherited disorder of cholesterol metabolism. This pathology is usually an autosomal dominant disorder and is caused by inherited mutations in the APOB, LDLR, and PCSK9 genes. Patients can have a homozygous or a heterozygous genotype, which determines the severity of the disease and the onset age of cardiovascular disease (CVD) manifestations. The incidence of heterozygous FH is 1: 200–250, whereas that of homozygous FH is 1: 100.000–160.000. Unfortunately, FH is often diagnosed too late and after the occurrence of a major coronary event. FH may be suspected in patients with elevated blood low-density lipoprotein cholesterol (LDL-C) levels. Moreover, there are other criteria that help to diagnose FH. For instance, the Dutch Lipid Clinical Criteria are a helpful diagnostic tool that is used to diagnose FH. FH often leads to the development of early cardiovascular disease and increases the risk of sudden cardiac death. Therefore, early diagnosis and treatment of this disease is very important. Statins, ezetimibe, bile acid sequestrants, niacin, PCSK9 inhibitors (evolocumab and alirocumab), small-interfering-RNA-based therapeutics (inclisiran), lomitapide, mipomersen, and LDL apheresis are several of the available treatment possibilities that lower LDL-C levels. It is important to say that the timeous lowering of LDL-C levels can reduce the risk of cardiovascular events and mortality in patients with FH. Therefore, it is essential to increase awareness of FH in order to reduce the burden of acute coronary syndrome (ACS).

Inclisiran—Safety and Effectiveness of Small Interfering RNA in Inhibition of PCSK-9

“…The diagnosis of FH is based in most cases on the clinical picture. Dutch Lipid Clinic Network criteria or, for example, WHO criteria are often used [ 105 , 106 ]. Moreover, in the diagnostic process, genetic testing is used.…”

Familial Hypercholesterolemia: A Literature Review of the Pathophysiology and Current and Novel Treatments

“…Statins are routinely used as therapeutic drugs reducing raised cholesterol levels. It acts mainly by inhibiting the HMG-CoA (hydroxy methyl glutaryl-coenzyme A) reductase enzyme, this enzyme regulates the overall metabolism of cholesterol in the body [ 15 ]. Statin blocks the active site in this enzyme.…”

“…This drug is sold under the trade name Leqvio [ 27 ]. The siRNA functions as a proprotein convertase inhibitor to prevent the translation of the protein PCSK9 [ 15 ]. Inclisiran use was approved in the European Union.…”

Synthesized Economic Evidence on the Cost-effectiveness of Screening Familial Hypercholesterolemia: A meta-analytic review and Aggregate Distributional Cost-Effectiveness Analysis

“…4 As a consequence, individuals with FH are predisposed to accelerated atherosclerotic cardiovascular disease (ASCVD) and coronary artery disease (CAD) development, which invariably augments their risk of premature mortality. 5 Classifications of FH differentiate between homozygous familial hypercholesterolemia (HoFH) and heterozygous familial hypercholesterolemia (HeFH). 6 Cumulatively, their global prevalence was historically estimated to be 1 in 500.…”

“…4 As a consequence, individuals with FH are predisposed to accelerated atherosclerotic cardiovascular disease (ASCVD) and coronary artery disease (CAD) development, which invariably augments their risk of premature mortality. 5…”