Discordance Between Apolipoprotein B and LDL-Cholesterol in Young Adults Predicts Coronary Artery Calcification. The CARDIA Study

Wilkins JT, Li RC, Sniderman A, et al.
J Am Coll Cardiol 2016;67:193–201

Background

The speed and quantity with which the arterial wall retains apolipoprotein B (apoB) containing particles depends on [1,2]: the permeability of the arterial endothelium, the plasma concentration of apoB containing particles and the binding affinity of the apoB particles to the collagen and elastin of the arterial wall.
LDL-C, non–HDL-C, and apoB predict CV risk equally well when the apoB particles contain an average amount of cholesterol. However, when the amount of cholesterol in the apoB particles deviates from this average, the predictive power of these markers differs [3]. Whereas augmented LDL-C and non-HDL-C levels have been associated with calcification of the coronary arterial wall [4], the association between apoB levels and coronary artery calcium (CAC) has not yet been evaluated.
The objective of this study is to investigate the associations between apoB and LDL-C and non-HDL-C and their potential value for the prediction of the long-term risk of developing calcification of the coronary arteries later in life. Specifically, discordance analysis was performed, in which biologically linked variables are analysed by groups of concordance or discordance between their relative distributions. This avoids that predictive powers in the discordant groups are attenuated by correlation between the markers of risk in concordant groups.
For this purpose the data of 2794 adults, aged 18 to 30 years, from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort were used [5,6]. ApoB values and CV risk stratification data were collected, as well as a CAC score after 25 years of follow-up (Y25).

Main results

• A clear inverse association between HDL-c and apoB was seen, as well as a direct relation between plasma TGs and apoB.
• About 9% of patients were in the discordant low apoB/high LCL-c (cholesterol enriched particles) and high apoB/low LDL-c (cholesterol-depleted particles) groups.
  Small but significant differences in waist circumference, BMI and percent obese were seen when comparing the 4 apoB/LDL-C concordance/discordance groups at baseline, with higher values in the higher apoB groups.
• Higher odds of developing Y25 CAC were seen in the middle apoB tertile (OR: 1.53) and high tertile (OR: 2.28) compared with the lowest apoB tertile and based on traditional risk factor–adjusted models
• The odds of developing Y25 CAC >0 was associated with the combination of:
  - Low LDL-C and high apoB (OR: 1.55)
  - Low non-HDL-C and high apo B (OR: 1.45)
  - The odds of CAC >0 at Y25 were highest for individuals with high apoB/high LDL-C and high apoB/high non–HDLC, which were those with the highest numbers of apoB particles.

Conclusions

These data suggest that apoB may be an important marker of coronary artery disease risk in young adults, since it was independently associated with the development of coronary artery calcification later in life. The odds for CAC in midlife in groups with discordant lipid levels suggest that the risk for CAC is more strongly influenced by apoB than by LDL-c and non-HDL-c in early adulthood.
Further follow-up might provide insights into the role of apoB measurements in predicting cardiovascular events.

Find this article online at JACC

References

1. Tabas I, Williams KJ, Boren J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 2007;116:1832–44.
2. Barter PJ, Ballantyne CM, Carmena R, et al. Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel. J Intern Med 2006;259:247–58.
3. Sniderman AD, Lamarche B, Contois JH, et al. Discordance analysis and the Gordian Knot of LDL and non-HDL cholesterol versus apoB. Curr Opin Lipidol 2014;25:461–7.
4. Loria CM, Liu K, Lewis CE, et al. Early adult risk factor levels and subsequent coronary artery calcification: the CARDIA Study. J Am Coll Cardiol 2007;49:2013–20.
5. Friedman GD, Cutter GR, Donahue RP, et al. CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol 1988;41:1105–16.
6. Hughes GH, Cutter G, Donahue R, et al. Recruitment in the Coronary Artery Disease Risk Development in Young Adults (Cardia) Study. Control Clin Trials 1987;8:68S–73S.