Cholesteryl ester transfer protein and mortality in patients undergoing coronary angiography: the Ludwigshafen Risk and Cardiovascular Health study.
BACKGROUND
The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still open to debate. In the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial, inhibition of CETP in patients with high cardiovascular risk was associated with increased high-density lipoprotein levels but increased risk of cardiovascular morbidity and mortality. In this report, we present a prospective observational study of patients referred to coronary angiography in which CETP was examined in relation to morbidity and mortality.


RESULTS
CETP concentration was determined in 3256 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study who were referred to coronary angiography at baseline between 1997 and 2000. Median follow-up time was 7.75 years. Primary and secondary end points were cardiovascular and all-cause mortality, respectively. CETP levels were higher in women and lower in smokers, in diabetic patients, and in patients with unstable coronary artery disease, respectively. In addition, CETP levels were correlated negatively with high-sensitivity C-reactive protein and interleukin-6. After adjustment for age, sex, medication, coronary artery disease status, cardiovascular risk factors, and diabetes mellitus, the hazard ratio for death in the lowest CETP quartile was 1.33 (1.07 to 1.65; P=0.011) compared with patients in the highest CETP quartile. Corresponding hazard ratios for death in the second and third CETP quartiles were 1.17 (0.92 to 1.48; P=0.19) and 1.10 (0.86 to 1.39; P=0.46), respectively.


CONCLUSIONS
We interpret our data to suggest that low endogenous CETP plasma levels per se are associated with increased cardiovascular and all-cause mortality, challenging the rationale of pharmacological CETP inhibition.
Ritsch
Andreas
A
Department of Internal Medicine I, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. andreas.ritsch@i-med.ac.at
Scharnagl
Hubert
H
Eller
Philipp
P
Tancevski
Ivan
I
Duwensee
Kristina
K
Demetz
Egon
E
Sandhofer
Anton
A
Boehm
Bernhard O
BO
Winkelmann
Bernhard R
BR
Patsch
Josef R
JR
März
Winfried
W
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood*; D017023:Coronary Angiography / Q000706:statistics & numerical data*; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000401:mortality / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D016016:Proportional Hazards Models; D012017:Referral and Consultation / Q000706:statistics & numerical data; D012307:Risk Factors
D015415:Biomarkers; D053480:Cholesterol Ester Transfer Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D008074:Lipoproteins; D002097:C-Reactive Protein