Higher CETP concentration is linked to coronary plaques in familial hypercholesterolemia, but not independently after adjustment (J Clin Lipidol 2026)

Original title: Metabolic and functional aspects of high-density lipoproteins (HDL) in familial hypercholesterolemia with or without subclinical coronary atherosclerosis

J Clin Lipidol · 25 November 2025 · 5

Juliani FC, Freitas FR, Miname MH, Rocha VZ, Lima JMDHS, Freitas RAMS, Damasceno NRT, Krieger JE, Maranhão RC, Santos RD

In fifty-three genetically confirmed patients with heterozygous familial hypercholesterolemia, of whom twenty-seven had coronary plaques and 26 had no vessel abnormalities on coronary computed tomography angiography, researchers assessed whether HDL-related parameters, including cholesterol transfer to HDL, HDL antioxidant capacity, particle size and subfractions, and plasma CETP and LCAT concentrations, were associated with subclinical coronary artery disease. No differences emerged between groups in apoB, LDL cholesterol, lipoprotein(a), HDL-C, HDL subfractions, triglycerides, lipid transfer to HDL, antioxidant capacity, or LCAT and PON-1 activity, but CETP concentration was significantly higher in patients with plaques (P less than .008). However, only family history of early coronary artery disease (odds ratio 4.12, P equals .022) and tendinous xanthomas (odds ratio 3.65, P equals .040) were independently associated with plaques, so no HDL-related parameter including CETP remained independently significant after adjustment.

Original abstract

Background: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature coronary atherosclerosis. Functional aspects of high-density lipoprotein (HDL), including cholesterol transfer capacity, may contribute to cardiovascular risk heterogeneity in FH.

Objective: To investigate whether cholesterol transfer to HDL and other HDL-related parameters are associated with coronary artery disease (CAD) in patients with heterozygous FH (HeFH).

Methods: Fifty-three genetically confirmed FH patients (mean age: 49.2 years; 73.6% female) were included. Twenty-seven had plaques, while 26 had no vessel abnormalities as determined by coronary computed tomography angiography. The transfer of both unesterified and esterified cholesterol (UC and EC) to HDL, as well as HDL antioxidant capacity, particle size, and subfractions, plasma concentrations of cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT), and paraoxonase-1 (PON-1) activity were assessed.

Results: Family history of premature CAD (P < .028) and tendinous xanthomas (P = .014) were more frequent in those with plaques. No differences were found in apolipoprotein (apo) B, LDL-C, LDL-C year score, lipoprotein(a), non-HDL-C, apo A-I, HDL-C, HDL subfractions, or triglycerides. Transfer of lipids to HDL and antioxidant capacity did not differ between the groups. LCAT concentrations and PON-1 activity were also similar. In contrast, CETP concentration was higher in those with plaques (P < .008). However, only family history of early CAD (odds ratio [OR]: 4.12, 95% CI, 1.23-13.80, P = .022) and xanthomas (OR: 3.65, 95% CI, 1.06-12.60, P = .040) were independently associated with plaques.

Conclusion: Among patients with HeFH, no HDL-related parameter was independently associated with subclinical CAD.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.