ApoA-I not superior to HDL-c to predict coronary heart disease

Association of High-Density Lipoprotein-Cholesterol Versus Apolipoprotein A-I With Risk of Coronary Heart Disease: The European Prospective Investigation Into Cancer-Norfolk Prospective Population Study, the Atherosclerosis Risk in Communities Study, and the Women’s Health Study

Literature - Van Capelleveen JC, Bochem AE, Boekholdt M, et al. - JAHA 2017, Epub ahead of print

Main results

12.6% of the EPIC-Norfolk cohort experienced CHD.
HR for CHD events highest versus lowest HDL-c quartile was 0.34 (95% CI 0.30-0.39, P trend <0.001). Fully adjusted, this was 0.69 (95% CI 0.59-0.80, P trend <0.001).
HR for CHD events highest versus lowest apoA-I quartile was 0.55 (95% CI 0.49-0.62, P trend <0.001). Fully adjusted, this was 0.75 (95% CI 0.66-0.86, P trend <0.001).
In almost half of the patients, HDL-c quartile and apoA-I quartile were discordant.
Within each apoA-I quartile, higher HDL-c levels were associated with lower CHD risk. In contrast, within each HDL-c quartile, we did not find a consistent association between apoA-I and CHD risk. However, a trend towards increased CHD risk with higher apoA-I levels was observed in the middle HDL-c quartiles.
HDL-c levels within apo-I quartiles were inversely associated with CHD risk factors (all P<0.001). However, opposite was true for apoA-I levels within HDL-c quartiles: positive association with age, female sex, BMI, HbA1c, non-HDL-c, triglycerides, apoB, SBP and CRP (all P<0.001).
Validation with the ARIC study (19.3% CHD events) showed comparable results regarding CHD risk. Significant trends were seen for the majority of HDL-c and apoA-I quartiles for risk factors: male percentage, BMI, non-HDL-c, triglyceride, ApoB, SBP and metabolic syndrome.
Validation with the WHS study were done with tertiles because of the low number of CHD events (3.9%). Also here, similar results were obtained.

Conclusion

In the EPIC-Norfolk cohort, HDL-c and apoA-I were strongly and inversely associated with CHD risk. However, these associations were not interchangeable as apoA-I levels did not show a similar trend within HDL-c quartiles, while vice versa, this was. Therefore, apoA-I levels do not offer predictive information over and above HDL-c. In contrast, an unexpected trend was even observed towards increased risk in some apoA-I quartiles. This was supported by a positive association of apoA-I levels with CHD risk factors within all HDL-c quartiles. All observations were confirmed in two independent cohorts, suggesting biological relevant associations.

References

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