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2 October 2008
Apolipoproteins as markers for residual risk reduction of myocardial infarction - INTERHEART

A standardized case-control study of acute myocardial infarction (MI) in 12 461 cases and 14 637 age-matched (plus or minus 5 years) and sex-matched controls in 52 countries demonstrated that one non-fasting apolipoprotein B100 (ApoB)/apolipoprotein A1 (ApoA1) ratio was superior to any of the cholesterol ratios for estimating risk of acute MI in all ethnic groups, in both gender, and at all ages.

McQueen MJ, Hawken S, Wang X
Comments & References
As close to 24 hours after acute MI symptoms, plasma lipid, lipoprotein, and apolipoprotein concentrations were measured, followed by the calculation of cholesterol and apolipoprotein ratios. Odds ratios (OR) and 95% confidence intervals (CI), and population-attributable risks (PARs) were calculated for each measure overall and for each ethnic group by comparison of the four upper quintiles with the lowest quintile.
Main results
  • Apolipoprotein B100 (ApoB)/apolipoprotein A1 (ApoA1) ratio had the highest PAR (54%) and the highest OR with each 1 standard deviation (SD) difference (1.59, 95% CI 1·53–1·64).
  • PAR for the ratio of the low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) was 37%.
  • PAR for the total cholesterol/HDL-C ratio was 32%; this was substantially lower than that of the ApoB/ApoA1 ratio (p<0.0001).
  • The results were consistent across age, gender and ethnic group.


In every comparison in the INTERHEART study, the ApoB/ApoA1 ratio was substantially better as a marker of vascular disease than any of the cholesterol ratios — i.e, total cholesterol / HDL-C, non-HDL-C / HDL-C, and LDL-C / HDL-C.

ApoB and ApoA1 are better markers of vascular disease than are their cholesterol counterparts.
For the INTERHEART study, dyslipidemia was not defined solely by LDL-C but as the ratio of ApoB to ApoA1, (often referred to as the “bad” and “good” apolipoproteins, respectively), which is representative of the ratio of atherogenic apoliporotein B100-carrying lipoproteins (mostly VLDL and LDL) to atheroprotective HDL. The ApoB/ApoA1 ratio has been shown to account for half the PAR of MI compared to eight other modifiable risk factors (smoking, exercise, fruit and vegetables intake, ethanol, hypertension, diabetes, abdominal obesity, psychosocial).1,2

Each atherogenic lipoprotein particle contains one molecule of ApoB. By contrast with ApoB, no simple association exists between either ApoA1 and HDL particle number or HDL-C level, whereas the association with plasma triglycerides differs; increases in plasma triglycerides were associated with greater reductions in HDL-C than in ApoA1. The authors state that the discordance between HDL-C and ApoA1 suggests that the effects of core lipid exchange between the cholesterol-rich HDL-2 and VLDL are more prominent than any associated changes in HDL clearance.

In common with what is known about the pathophysiology of these particles3,4,5 at every tertile of the total cholesterol/HDL-C ratio, increasing ratios of ApoB/ApoA1 increased the risk of MI (Figure 1). By contrast, in the second and third tertiles of ApoB/ApoA1, increases in the ratios of total cholesterol/HDL-C were associated with a reduced risk of MI.

Introducing ApoB test into worldwide clinical practice
This study supports ApoB and ApoA1 as better markers of vascular disease than their cholesterol counterparts. Indeed, the American Diabetes Association and the American College of Cardiology3 have stated that ApoB is the test of choice to assess the adequacy of statin therapy in lowering LDL-C and should therefore be introduced into routine clinical practice. Apolipoprotein measurements are well standardized, simple and inexpensive and can be done with samples obtained from fasting or non-fasting individuals.

Taking this together with the findings of this study, ApoB and ApoA1 could represent key modifiable factors as well as follow-up variables in residual risk reduction of cardiovascular disease.


Figure 1 Odds ratio (95% CI) of myocardial infarction by tertiles for apolipoprotein B100 (ApoB)/ apolipoprotein A1 (ApoA1)
and total cholesterol (TC)/HDL cholesterol (HDL C) ratios

  1. Lamarche B, Moorjani S, Lupien PJ, et al. Circulation 1996;94: 273–78.
  2. Pyorala K, Pedersen TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirsson G. Diabetes Care 1997;20: 614–20.
  3. Barter PJ, Ballantyne CM, Carmena R, et al. J Intern Med 2006;259: 247–58.
  4. Walldius G, Junger I. J Intern Med 2006;259: 493–519.
  5. Tremblay AJ, Sniderman AD, Gagné C, Bergeron J, Couture P. Clin Biochem 2007;40: 25–29.