Homozygous Familial Hypercholesterolemia Is a Life-Limiting Condition Medical Life-Trajectories in the Post-2010 Era
| Authors | |
|---|---|
| Year of publication | 2025 |
| Type | Article in Periodical |
| Magazine / Source | JACC-JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY |
| MU Faculty or unit | |
| Citation | |
| web | https://www.sciencedirect.com/science/article/pii/S0735109725061674?pes=vor&utm_source=clarivate&getft_integrator=clarivate |
| Doi | https://doi.org/10.1016/j.jacc.2025.04.005 |
| Keywords | ASCV D; cardiovascular disease; homozygous familial hypercholesterolemia; LDL-cholesterol; mortality |
| Attached files | |
| Description | Homozygous familial hypercholesterolemia (HoFH) is a rare (~1:360,000) genetic disorder characterized by extremely high low-density lipoprotein cholesterol (LDL-C) levels, leading to premature atherosclerotic cardiovascular disease (ASCVD) and early death. HoFH is typically caused by bi-allelic pathogenic variants in low-density lipoprotein receptor (LDLR), APOB, and/or PCSK9 genes via a semidominant inheritance pattern, while LDLRAP1 pathogenic variants cause a rare recessive form. Phenotypic severity is generally correlated with residual LDLR function. Lipid-lowering treatment (LLT) is initiated with a combination of high-intensity statin and ezetimibe, followed by a trial of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor therapy, which is continued if LDL-C reduction is >15%. If LDL-C goals remain unmet, LDLR-independent drugs, apheresis, or rarely liver transplantation are pursued.1 Despite combination LLT, most patients with HoFH do not reach guideline-recommended LDL-C goals. Data on life-courses largely stem from older case reports and case series when more recent LLT were not available. We describe characteristics and clinical courses of HoFH patients under contemporary care, with particular focus on deceased patients. |
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