The class
Genetic CETP deficiency review: heterozygotes have lower ASCVD risk, homozygotes show no excess risk, and very high HDL-C raises AMD questions (J Atheroscler Thromb 2025)
Original title: Cholesteryl Ester Transfer Protein Deficiency and Hyperalphalipoproteinemia
A review comparing the lipoprotein phenotypes of genetic CETP deficiency with those achieved by pharmacological CETP inhibitors, and their relationship to atherosclerotic cardiovascular disease (ASCVD) and age-related macular degeneration (ARMD). In carriers of CETP-truncating variants with reduced LDL-C, heterozygotes had decreased ASCVD risk, while ASCVD prevalence was not increased in homozygotes with CETP deficiency. The author argues the association between ASCVD and ARMD risk in multifactorial hyperalphalipoproteinaemia, where HDL-cholesterol exceeds 100 mg/dL, still needs an etiological basis before being generalised to drug-induced HDL elevation. The review summarises the historical hurdles facing CETP inhibitor development, incorporating recent obicetrapib findings as context rather than as new data of its own.
Original abstract
Cholesteryl ester transfer protein (CETP) deficiency and lipoprotein phenotypes with CETP inhibitors were compared. The effects on atherosclerotic cardiovascular disease (ASCVD) and the recently suggested retinal disease of age-related macular degeneration (ARMD) were summarized and discussed in relation to CETP deficiency and extremely increased high-density lipoprotein (HDL) cholesterol levels (＞100 mg/dL). In CETP truncated variants leading to reduced low-density lipoprotein cholesterol levels, ASCVD risk was decreased in heterozygotes. ASCVD prevalence did not increase in homozygotes with CETP deficiency. However, the association between ASCVD and ARMD risks in cases of very high HDL cholesterol level found in multifactorial hyperalphalipoproteinemia needs to be clarified on an etiological basis. The hurdles facing the development of CETP inhibitors are summarized, including a new result for obicetrapib.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.