Management of Familial Hypercholesterolemia: A Review of the Recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia

Abstract

suMMaRyFamilial hypercholesterolemia (FH) is a genetic disorder of lipid metabolism that is characterized by a significant elevation in levels of low-density lipoprotein cholesterol (LDL-C), and patients are at very high risk for premature coronary heart disease (CHD). The etiology of FH includes known mutations in the gene of the LDL receptor, LDLR ; the gene of apolipoprotein B, apo B ; and the proprotein convertase subtilisin/kexin type 9 gene, PCSK9. The National Lipid Association Expert Panel on Familial Hypercholesterolemia has provided recommendations for the screening and treatment of patients with FH. Early identification and aggressive treatment of FH in individual patients, as well as screening of all first-degree relatives, are recommended to minimize the risk for premature CHD. Similar to patients with conventional hypercholesterolemia, patients with FH should receive statins as initial treatment, but patients with FH may require higher doses of statins, more potent statins, statin-based combination therapy, or adjunctive therapies. Patients with FH who have additional risk factors for, or existing, cardiovascular disease or those with an inadequate response to initial statin therapy should have access to higher doses of the most efficacious statins; statins used in combination with other LDL-C-lowering agents should also be supported by formularies; additional treatments, such as LDL-C apheresis or novel therapies, may also be required to achieve acceptable LDL-C levels. New treatment approaches include mipomersen, which was approved by the FDA in January 2013. Mipomersen is an oligonucleotide inhibitor of apolipoprotein B-100 synthesis (called an antisense inhibitor) indicated as an adjunct to lipid-lowering medications and diet to reduce LDL-C, apolipoprotein B, total cholesterol, and non-high density lipoproteincholesterol (non-HDL-C) levels in patients with homozygous FH (HoFH). The microsomal transfer protein lomitapide has also received FDA approval for use only in patients with HoFH. Other novel treatments currently in development include PCSK9 inhibitors. Therapies such as apheresis are likely more expensive than simple therapy with a statin but may be needed to achieve long-term reductions in complications from nonfatal and fatal cardiovascular events and hospitalizations related to myocardial infarction, cardiac revascularization, and stroke in FH patients. The cost-effectiveness of this more aggressive therapy has not been determined and should be studied. Utilization of published guidelines and the recommendations from the National Lipid Association will help to optimize the management of patients with FH.

Towards a European consensus for reporting incidental findings during clinical NGS testing

“…Results that are actionable on reproductive grounds, for example, carrier status of a heterozygous CFTR mutation in a child investigated for development delay. Are personally actionable, entailing lifestyle change and the reduction of risk factors, for example, familial hypercholesterolaemia 28 or MCAD deficiency.…”

Šeiminė Hipercholesterolemija

“…ir 12,5 proc. [31]. Pakopinio tyrimo esmė -paciento, kuriam diagnozuota ŠH, visų pirmos eilės šeimos narių ištyrimas, o nustačius ligą šeimos nariui, numatomas visų jo pirmos eilės giminaičių ištyrimas [31].…”

“…[31]. Pakopinio tyrimo esmė -paciento, kuriam diagnozuota ŠH, visų pirmos eilės šeimos narių ištyrimas, o nustačius ligą šeimos nariui, numatomas visų jo pirmos eilės giminaičių ištyrimas [31]. Efektyviausias tyrimo būdas -genetinis ištyrimas, priešingai nei vien cholesterolio koncentracijos nustatymas, kuris nėra specifiškas [32].…”

Consenso sobre manejo de las dislipidemias en pediatría

“…En nuestro medio, los médicos pediatras especialistas en Nutrición infantil serían los recomendados. 14,30,31 Los fármacos utilizados en el tratamiento de las dislipidemias se agrupan de la siguiente manera:…”