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.