Physicians' Academy for Cardiovascular Education

Type and dose of treatment affects the correlation between apoB and LDL-c or non-HDL-c

Literature - Farnier M, Guyton JR, Jensen E, et al. - Atherosclerosis. 2013 Aug;229(2):415-22

Effects of ezetimibe, simvastatin and ezetimibe/simvastatin on correlations between apolipoprotein B, LDL cholesterol and non-HDL cholesterol in patients with primary hypercholesterolemia.

Farnier M, Guyton JR, Jensen E, et al.
Atherosclerosis. 2013 Aug;229(2):415-22. doi: 10.1016/j.atherosclerosis.2013.05.010


In addition to LDL-c, non-HDL-c and apolipoprotein B (apoB) have been proposed as targets of drug therapy, and levels of the latter two may provide a more accurate assessment of future coronary risk than does LDL-c [1-6]. Many statin-treated patients still have a remaining increased risk , partly due to elevated apoB-containing lipoprotein particles [7,8], particularly in patients with metabolic syndrome, hypertriglyceridemia, and/or type 2 diabetes mellitus (T2DM). In patients who do not reach recommended LDL-c levels, additional lipid-lowering agents may be required.
Ezetimibe (EZE) blocks cholesterol absorption and can give additional lipid and lipoprotein reductions when added to statin therapy [9-12]. LDL-c, non-HDL-c and apoB are not affected to a similar extent by both statins and EZE. It is unclear how different combination therapies affect the correlations between apoB and LDL-c or non-HDL-c. This posthoc analysis therefore compares the correlations between apoB:LDL-c and apoB:non-HDL-c in a large population (n=2990) of untreated hypercholesterolemic patients, both at baseline and following 12 weeks of treatment with placebo, EZE, simvastatin (SIMVA) or EZE/SIMVA.

Main results

  • EZE/SIMVA was more efficient than SIMVA alone with regard to lowering LDL-c, non-HDL-c and apoB at each dose comparison.
  • ApoB was less strongly reduced than were LDL-c and non-HDL-c, after EZE, SIMVA or EZE/SIMVA.
  • LDL-c and non-HDL-c strongly correlated with apoB in all treatment groups, at both baseline and endpoint, with the strongest correlation for non-HDL-c and apoB.
  • Correlations between apoB:LDL-c (r>0.88) and apoB:non-HDL-c (r>0.94) were generally stronger after treatment with lipid-lowering therapy, as compared to baseline (r>0.76 for LDL-c and r>0.86 for non-HDL-c), specifically with SIMVA and EZE/SIMVA, and with increasing dose.
  • Predicted values of LDL-c and non-HDL-c for a known apoB level (80 mg/dl) were calculated from a linear regression model. In untreated patients these predicted values were similar across treatment groups. After treatment with SIMVA and EZE/SIMVA, LDL-c and non-HDL-c were lower than after EZE and placebo. In a comparison based on triglyceride levels (higher or lower than 200 mg/dL), predicted LDL-c values were generally lower in patients with high TG levels, both at baseline and after treatment, irrespective of treatment. In contrast, non-HDL-c levels were often higher in high TG vs low TG patients, mostly at baseline.
  • 63-79% of people in the SIMVA group and 51-68% in the EZE/SIMVA group achieved LDL-c and non-HDL-c recommendations as well as an apoB < 80 mg/dL. However, a large part of the patients who received SIMVA or EZE/SIMVA kept apoB>80 mg/dL, despite reaching LDL-c <70 mg/dL and non-HDL-c <100mg/dL.


The type and potency of treatment affects the correlations between apoB and LDL-c or non-HDL-c, and correlations were generally stronger in patients with low TG levels, irrespective of type of treatment. Many patients who achieved the most stringent LDL-c and non-HDL-c levels still had apoB>80 mg/dL, while the majority of patients who reached the apoB target had also met LDL-c and non-HDL-c recommendations. LDL-c may thus not be the best indicator of treatment-induced changes. Patients may remain at increased risk due to insufficient apoB-lowering even when receiving high doses of SIMVA or combination therapy.


1. Boekholdt SM, Arsenault BJ, Mora S, et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA 2012;307: 1302e9.
2. Ingelsson E, Schaefer EJ, Contois JH, et al. Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. JAMA 2007;298:776e85.
3.  Liu J, Sempos CT, Donahue RP, Dorn J, Trevisan M, Grundy SM. Non-highdensity lipoprotein and very-low-density lipoprotein cholesterol and their risk predictive values in coronary heart disease. Am J Cardiol 2006;98:
4. Pischon T, Girman CJ, Sacks FM, Rifai N, Stampfer MJ, Rimm EB. Non-highdensity lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men. Circulation 2005;112:3375e83.
5. Robinson JG, Wang S, Smith BJ, Jacobson TA. Meta-analysis of the relationship between non-high-density lipoprotein cholesterol reduction and coronary heart disease risk. J Am Coll Cardiol 2009;53:316e22.
6. Sniderman AD, Williams K, Contois JH, et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes 2011;4:337e45.
7.Davidson MH. Reducing residual risk for patients on statin therapy: the potential role of combination therapy. Am J Cardiol 2005;96:3Ke13K.
8. Fruchart JC, Sacks FM, Hermans MP, et al. The residual risk reduction initiative: a call to action to reduce residual vascular risk in dyslipidaemic patient. Diab Vasc Dis Res 2008;5:319e35.
9. Bays HE, Ose L, Fraser N, et al. A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Clin Ther 2004;26:1758e73.
10. Davidson MH, McGarry T, Bettis R, et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol 2002;40:2125e34.
11. Davidson MH, Ballantyne CM, Kerzner B, et al. Efficacy and safety of ezetimibe coadministered with statins: randomised, placebo-controlled, blinded experience in 2382 patients with primary hypercholesterolemia. Int J Clin Pract 2004;58:746e55.
12. Goldberg AC, Sapre A, Liu J, Capece R, Mitchel YB. Efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc 2004;79:620e9.

Find this article on Pubmed