Apolipoprotein A-II is inversely associated with risk of future coronary artery disease.

Abstract

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.

METHODS AND 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.

• Authors: Rakesh S Birjmohun, Geesje M Dallinga-Thie, Jan Albert Kuivenhoven, Erik S G Stroes, James D Otvos, Nicholas J Wareham, Robert Luben, John J P Kastelein, Kay-Tee Khaw, S Matthijs Boekholdt
• Journal: Circulation (Circulation) Vol. 116 Issue 18 Pg. 2029-35 (Oct 30 2007) ISSN: 1524-4539 [Electronic] United States
• PMID: 17923573 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein A-II

Topics

• Aged
• Apolipoprotein A-II (blood)
• Case-Control Studies
• Coronary Artery Disease (blood, epidemiology, prevention & control)
• Female
• Follow-Up Studies
• Forecasting
• Humans
• Male
• Middle Aged
• Prospective Studies
• Risk Factors