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What is new in familial hypercholesterolemia?

Santos, Raul D.; Maranhao, Raul C.

Current Opinion in Lipidology: June 2014 - Volume 25 - Issue 3 - p 183–188
doi: 10.1097/MOL.0000000000000073
LIPID METABOLISM: Edited by Ernst J. Schaefer

Purpose of review The purpose of this review is to describe advances in the diagnosis, cause, metabolism, risk factors for atherosclerosis, and treatment of familial hypercholesterolemia.

Recent findings Heterozygous familial hypercholesterolemia is almost four-fold more frequent than previously thought and is associated with 10-fold to 13-fold risk of cardiovascular disease comparing with normolipidemics. LDL receptor (LDLR) dysfunction and LDL-cholesterol (LDL-C) accumulation disturb the metabolism of other lipoprotein classes, such as chylomicrons and remnants and HDL. Next-generation sequencing can improve familial hypercholesterolemia molecular diagnosis due to its better performance and lower costs than usual techniques. Despite this, roughly 40% of familial hypercholesterolemia patients do not present mutations on the LDLR, apolipoprotein B, or proprotein convertase subtilisin/kexin type 9 genes. Many individuals with familial hypercholesterolemia phenotype have polygenic instead of monogenic cause of their elevated LDL-C concentrations. Individuals with familial hypercholesterolemia show elevated burden of subclinical atherosclerosis. The intensity of atherosclerosis burden is associated with the severity of LDLR mutation rather than maternal or paternal heritability. Newer-approved and on-development medications that reduce LDL-C hold promise for preventing cardiovascular disease in familial hypercholesterolemia.

Summary Familial hypercholesterolemia is frequent and currently underdiagnosed and undertreated, but effective cascade screening programs and early and intensive LDL-C lowering can change this picture and the natural history of the disease.

Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil

Correspondence to Raul D. Santos, Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Av Dr Eneas C. Aguiar, 44 Segundo Andar Bloco 2, Sala 4, 05403-900 Sao Paulo, Brazil. Tel: +55 11 26615320; fax: +55 11 26615017; e-mail:,

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins