CETP activity, but not mass, is independently linked to coronary disease in patients with high HDL cholesterol (Anatol J Cardiol 2026)

Original title: Dissociation Between Cholesteryl Ester Transfer Protein Mass and Activity in Coronary Artery Disease Patients with Elevated High-Density Lipoprotein Cholesterol: Implications for High-Density Lipoprotein Function and Residual Cardiovascular Risk

Anatol J Cardiol · 27 April 2026 · 7

Kunak T, Ülgen Kunak A, Abacı A

Since some patients with coronary artery disease present with elevated HDL cholesterol despite HDL's traditional cardioprotective reputation, researchers compared CETP mass and activity, apolipoproteins, and HDL subclasses between 35 coronary artery disease patients and 35 age- and lipid-matched controls, all with HDL cholesterol of 60 mg/dL or higher and LDL cholesterol of 130 mg/dL or higher. CETP activity was significantly higher in coronary artery disease patients than controls (1.08 versus 0.98 nmol per microlitre per hour, P equals .007), while CETP mass, HDL2 and HDL3 levels were similar between groups, and apolipoprotein A-I was paradoxically higher in patients (P equals .006). In multivariate analysis adjusting for age and sex, CETP activity remained independently associated with coronary artery disease (odds ratio 2.03, 95% CI 1.27 to 3.24, P equals .002), suggesting CETP function rather than mass contributes to residual cardiovascular risk and that HDL quality matters more than quantity for atheroprotection.

Original abstract

Background: High-density lipoprotein cholesterol (HDL-C) is traditionally viewed as cardioprotective; however, some patients with coronary artery disease (CAD) may present with elevated HDL-C levels, challenging this assumption. This study aimed to investigate the roles of HDL subclasses, apolipoproteins, and cholesteryl ester transfer protein (CETP) activity and mass in patients with CAD with high HDL-C and low-density lipoprotein cholesterol (LDL-C) levels.

Methods: A total of 35 patients with CAD and 35 age- and lipid-matched control participants (HDL-C ≥ 60 mg/dL and LDL-C ≥ 130 mg/dL) were enrolled. Cholesteryl ester transfer protein mass and activity, apolipoprotein A-I (ApoA-I), ApoA-II, ApoB, and HDL subclasses (HDL2 and HDL3) were measured and compared between groups. Correlation analyses and multivariate logistic regression were performed to assess the relationship between CETP activity and CAD.

Results: The CETP activity was significantly higher in patients with CAD compared with control participants (1.08 vs. 0.98 nmol/μL/h, P = .007), whereas CETP mass, HDL2, and HDL3 levels were similar. The ApoA-I levels were paradoxically higher in patients with CAD (P = .006), with no differences in ApoA-II or ApoB. In multivariate analysis, CETP activity remained independently associated with CAD after adjusting for age and sex (OR 2.03; 95% CI 1.27-3.24; P = .002).

Conclusion: In patients with high HDL-C and LDL-C, increased CETP activity-but not mass-was associated with the presence of CAD, suggesting CETP function may con-tribute to residual cardiovascular risk. Elevated ApoA-I levels in patients with CAD may reflect dysfunctional HDL, emphasizing that HDL quality, rather than quantity, plays a more critical role in atheroprotection. These findings support a functional evaluation of lipoproteins in cardiovascular risk assessment.

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