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. 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.