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.
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).


CONCLUSIONS
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.
Department of Endocrinology, University Medical Center Groningen and University of Groningen, 9700 RB Groningen, The Netherlands.
Paul J W H
PJ
Kappelle
Ron T
RT
Gansevoort
Hans J
HJ
Hillege
Bruce H R
BH
Wolffenbuttel
Robin P F
RP
Dullaart
D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood*; D001055:Apolipoproteins B / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002784:Cholesterol / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D002784:Cholesterol