Common CETP genetic variants do not alter how well the apoB/apoA-I ratio predicts first major cardiovascular events compared with TC/HDL-C (J Clin Lipidol 2012)

Original title: Common variation in cholesteryl ester transfer protein: relationship of first major adverse cardiovascular events with the apolipoprotein B/apolipoprotein A-I ratio and the total cholesterol/high-density lipoprotein cholesterol ratio

J Clin Lipidol · 22 May 2012 · 6

Kappelle PJ, Gansevoort RT, Hillege HJ, Wolffenbuttel BH, Dullaart RP, PREVEND Study Group

In the PREVEND case-cohort study of 6,780 subjects free of cardiovascular disease and lipid-lowering drugs at baseline, researchers tested whether common CETP variants (TaqIB and -629C to A) modified the predictive strength of the apoB/apoA-I ratio versus the total cholesterol/HDL cholesterol ratio for a first major adverse cardiovascular event (MACE). Over 10.8 years of follow-up, 532 of 6,780 subjects experienced a first MACE, with age- and sex-adjusted hazard ratios of 1.31 (95% CI 1.23 to 1.41) for apoB/apoA-I and 1.22 (95% CI 1.26 to 1.39) for TC/HDL-C, both P less than .001. These relationships were essentially unchanged within each CETP genotype group, with no significant interactions detected (P greater than .20 for all), indicating CETP genetic variation does not modify which lipid ratio best predicts cardiovascular risk.

Original abstract

Background: The preference of the apolipoprotein (apo) B/apoA-I ratio over the total cholesterol/HDL cholesterol (TC/HDL-C) ratio in cardiovascular risk prediction is disputed. Cholesteryl ester transfer protein (CETP) is instrumental in lipoprotein remodelling and affects the cholesterol content in pro- and antiatherogenic lipoproteins relative to their major apolipoproteins. We tested the influence of common CETP variations on the strength of associations of a first major adverse cardiovascular event (MACE) with the apoB/apoA-I ratio compared with the TC/HDL-C ratio.

Methods: A prospective case-cohort study was performed (PREVEND cohort; no previous cardiovascular disease and no use of lipid-lowering drugs initially). Fasting serum TC/HDL-C, apoB/apoA-I, triglycerides, and common CETP variations (TaqIB [rs708272] and -629C>A [rs1800775] polymorphisms) were measured at baseline. The composite end point was incident MACE.

Results: A total of 532 of 6780 subjects experienced a first MACE during 10.8 years follow-up. The age- and sex-adjusted hazard ratio was 1.31 (95 % confidence interval 1.23-1.41) for the apoB/apoA-I ratio and 1.22 (95% confidence interval 1.26-1.39) for the TC/HDL-C ratio (both P < .001). These relationships were essentially similar within each TaqIB and -629C>A CETP genotype group. No interactions of the apoB/apoA-I ratio and the TC/HDL-C ratio with the TaqIB and the -629C>A CETP variations on incident MACE were observed (P > .20 for all).

Conclusion: The relationship of first MACE with the TC/HDL-C and the apoB/apoA-I ratio is not to an important extent dependent on common CETP variations. CETP variations are unlikely to affect the strength of the relationship of first MACE with the apoB/apoA-I ratio compared with the TC/HDL-C ratio.

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