Plasma levels of cholesteryl ester transfer protein and the risk of future coronary artery disease in apparently healthy men and women: the prospective EPIC (European Prospective Investigation into Cancer and nutrition)-Norfolk population study.
BACKGROUND
Low plasma levels of cholesteryl ester transfer protein (CETP) are associated with elevated levels of HDL cholesterol (HDL-C), but it remains unclear whether this translates into a concomitant reduction in the risk of coronary artery disease (CAD). Evidence exists that the effect of CETP depends on metabolic context, in particular on triglyceride levels.


RESULTS
A nested case-control study was performed in the prospective EPIC-Norfolk cohort study. Cases were apparently healthy men and women aged 45 to 79 years who developed fatal or nonfatal CAD during follow-up. Control subjects were matched by age, sex, and enrollment time. CETP levels were not significantly different between cases and controls (4.0+/-2.2 versus 3.8+/-2.1 mg/L, P=0.07). CETP levels were significantly related to plasma levels of total cholesterol, LDL cholesterol, and HDL-C. The risk of CAD increased with increasing CETP quintiles (P for linearity=0.02), such that subjects in the highest quintile had an adjusted OR of 1.43 (95% CI 1.03 to 1.99, P=0.03) versus those in the lowest. Among individuals with triglyceride levels below the median (1.7 mmol/L), no relationship between CETP levels and CAD risk was observed (P for linearity=0.5), but this relationship was strong among those with high triglyceride levels (P for linearity=0.02), such that those in the highest CETP quintile had an OR of 1.87 (95% CI 1.06 to 3.30, P=0.02).


CONCLUSIONS
Elevated CETP levels are associated with an increasing risk of future CAD in apparently healthy individuals, but only in those with high triglyceride levels.
Boekholdt
S Matthijs
SM
Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
Kuivenhoven
Jan-Albert
JA
Wareham
Nicholas J
NJ
Peters
Ron J G
RJ
Jukema
J Wouter
JW
Luben
Robert
R
Bingham
Sheila A
SA
Day
Nicholas E
NE
Kastelein
John J P
JJ
Khaw
Kay-Tee
KT
D000368:Aged; D002352:Carrier Proteins / Q000097:blood*; D016022:Case-Control Studies; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D015897:Comorbidity; D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012306:Risk; D012907:Smoking / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006023:Glycoproteins; D014280:Triglycerides