Abstract 1633: ApolipoproteinA-II is Inversely Associated with Risk of Future Coronary Artery Disease
Background: The protective role of apolipoproteinA-I (apoA-I) on atherosclerosis has been substantiated extensively. In contrast, apoA-II enriched HDL has been suggested to have poor anti-atherogenic properties, mostly in small experimental studies. However, large observational studies in humans are still lacking. Presently, we evaluated in a large-scaled prospective study whether apoA-II concentration is associated with risk of future coronary artery disease (CAD).
Methods and Results: We performed a case-control study nested in the prospective EPIC-Norfolk cohort. Cases (n=951) 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. Controls (n=1883) were matched by age, sex, and enrollment time. Conditional logistic regression was used to quantify the relationship between apoA-II levels and risk of CAD. Plasma apoA-II concentration was significantly lower in cases (34.6 mg/dl) vs. controls (35.2 mg/dl). Elevated apoA-II levels were associated with a decreased risk of CAD such that people in the top apoA-II quartile (> 38.3 mg/dl) had an odds ratio (OR) of 0.60 (95% CI 0.47 to 0.77) vs. those in the lowest quartile (<31.2 mg/dl; p for linearity <0.0001). After adjustment for traditional risk factors (body mass index, smoking, diabetes, systolic blood pressure, LDL-c, HDL-c, triglycerides and CRP), the corresponding risk estimate was 0.49 (95% CI 0.35 to 0.69, p for linearity <0.0001). Interestingly, even upon additional adjustment for apoA-I and HDL particle number, elevated apoA-II levels were still independently associated with the risk of future CAD: OR 0.64 (95% CI 0.44 to 0.92, p for linearity =0.025) in the top vs. lowest quartile.
Conclusions: Low levels of apoA-II are associated with an increased risk of future CAD in apparently healthy subjects. These prospective data for the first time demonstrate a strong, inverse relation between apoA-II levels and risk of future CAD events.