Apolipoprotein A-II is inversely associated with risk of future coronary artery disease.
BACKGROUND
Although the vasculoprotective effects of apolipoprotein A-I (apoA-I), the major protein associated with high-density lipoprotein, have been universally accepted, apoA-II has been suggested to have poor antiatherogenic or even proatherogenic properties. To study this suggestion more closely, we evaluated how serum levels of apoA-II and apoA-I relate to the risk of future coronary artery disease (CAD) in a large, prospective study.


RESULTS
We performed a nested case-control study in the prospective EPIC-Norfolk (European Prospective Investigation into Cancer and Nutrition-Norfolk) cohort. Case subjects (n=912) were apparently healthy men and women aged 45 to 79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Control subjects (n=1635) were matched by age, gender, and enrollment time. Conditional logistic regression was used to quantify the relationship between serum apoA-II levels and risk of CAD. Serum apoA-II concentration was significantly lower in case subjects (34.5+/-6.3 mg/dL) than in control subjects (35.2+/-5.8 mg/dL) and was inversely associated with risk of CAD, such that patients in the upper quartile (>38.1 mg/dL) had an odds ratio of 0.59 (95% confidence interval 0.46 to 0.76) versus those in the lowest quartile (<31.1 mg/dL; P for linearity <0.0001). After adjustment for fasting time, alcohol use, and cardiovascular risk factors (systolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, body mass index, smoking, diabetes mellitus, and C-reactive protein), the corresponding risk estimate was 0.48 (95% confidence interval 0.34 to 0.67, P for linearity <0.0001). Surprisingly, additional adjustment for serum apoA-I levels did not affect risk prediction of apoA-II for future CAD (odds ratio 0.49, 95% confidence interval 0.34 to 0.68, P for linearity <0.0001). Also, after adjustment for high-density lipoprotein particle number and size, apoA-II was still associated with the risk of future CAD (odds ratio 0.62, 95% confidence interval 0.43 to 0.90, P for linearity 0.02).


CONCLUSIONS
ApoA-II is associated with a decreased risk of future CAD in apparently healthy people. These findings imply that apoA-II itself exerts effects on specific antiatherogenic pathways. On the basis of these findings, discussion of the potential proatherogenic effects of apoA-II can cease.
Birjmohun
Rakesh S
RS
Academic Medical Center, Department of Vascular Medicine, 1100 DD, Amsterdam, The Netherlands.
Dallinga-Thie
Geesje M
GM
Kuivenhoven
Jan Albert
JA
Stroes
Erik S G
ES
Otvos
James D
JD
Wareham
Nicholas J
NJ
Luben
Robert
R
Kastelein
John J P
JJ
Khaw
Kay-Tee
KT
Boekholdt
S Matthijs
SM
D000368:Aged; D016633:Apolipoprotein A-II / Q000097:blood*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
D016633:Apolipoprotein A-II