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The strengths and limitations of the ApoB/ApoA-I ratio to predict the risk of vascular disease: a hegelian analysis

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Abstract

The levels of pro-and antiatherogenic lipoproteins are the most important risk factors for vascular disease, and there is now compelling evidence that the apolipoprotein (apo) B/apoA-I ratio is a better index of the likelihood of vascular events than any of the corresponding cholesterol indices: the total cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio, non-HDL-C/HDL-C ratio, or low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio. But are there any restrictions on the application of the apoB/apoA-I ratio to clinical practice? This article suggests that the answer is yes. Based on the available biologic and epidemiologic data, the relation between risk and apoB is continuous, whereas at the extremes of HDL concentration in plasma the relation to risk is not certain. Moreover, LDL plays a causal role in atherogenesis whereas HDL plays a contingent role. Appreciating these distinctions should allow appropriate use of the apoB/apoA-I ratio as a simple, single, summary index of the lipoprotein-related risk of vascular disease.

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References and Recommended Reading

  1. Barter PJ, Ballantyne CM, Carmena R, et al.: ApoB versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel. J Intern Med 2006, 259:247–258.

    Article  PubMed  CAS  Google Scholar 

  2. Thompson A, Danesh J: Associations between apolipoprotein B, apolipoprotein AI, the apolipoprotein B/AI ratio and coronary heart disease: a literature-based meta-analysis of prospective studies. J Intern Med 2006, 259:481–492.

    Article  PubMed  CAS  Google Scholar 

  3. Dunbar RL, Rader DJ.: Measurement of atherogenic lipoproteins in cardiovascular risk assessment. In Contemporary Cardiology: Cardiovascular Biomarkers: Pathophysiology and Disease Management. Edited by Morrow DA. Totowa, NJ: Humana Press; 2006:497–517.

    Google Scholar 

  4. Chan DC, Watts GF: Apolipoproteins as markers and managers of coronary risk. QJ Med 2006, 99:277–287.

    CAS  Google Scholar 

  5. Walldius G, Jungner I: The apoB/apoA-1 ratio: a strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy—a review of the evidence. J Intern Med 2006, 259:493–519.

    Article  PubMed  CAS  Google Scholar 

  6. Benn M, Nordestgaard BG, Jensen GB, Tybjaerg-Hansen A: Improving prediction of ischemic cardiovascular disease in the general population using apolipoprotein B: the Copenhagen City Heart Study. Aterioscler Thromb Vasc Biol 2007, 27:661–670.

    Article  CAS  Google Scholar 

  7. Gotto AM, Whitney E, Stein EA, et al.: Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation 2000, 101:477–484.

    PubMed  CAS  Google Scholar 

  8. van Lennep JE, Westerveld HT, van Lennep HW, et al.: Apolipoprotein concentrations during treatment and recurrent coronary artery disease events. Arterioscler Thromb Vasc Biol 2000, 20:2408–2413.

    PubMed  Google Scholar 

  9. Simes RJ, Marschner IC, Hunt D, et al.: Relationship between lipid levels and clinical outcomes in the long-term intervention with pravastatin in the ischemic disease (LIPID) trial. To what extent is the reduction in coronary events with pravastatin explained by on-study lipid levels? Circulation 2002, 105:1162–1169.

    Article  PubMed  CAS  Google Scholar 

  10. Nicholls SJ, Tuzcu EM, Sipahi I, et al.: Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA 2007, 297:499–508.

    Article  PubMed  CAS  Google Scholar 

  11. Kastelein JJ, Holme I, Barter P, et al.: Superiority of apoB/apoAI ratio for predicting cardiovascular risk in pooled analyses of the incremental decrease in endpoints through aggressive lipid-lowering (IDEAL) and treating to new targets (TNT) trials. Circulation 2006, II:713.

    Google Scholar 

  12. Walldius G, Jungner I, Aastveit AH, et al.: The apoB/apoA-I ratio is better than the cholesterol ratios to estimate the balance between the plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk. Clin Chem Lab Med 2004, 42:1355–1363.

    Article  PubMed  CAS  Google Scholar 

  13. Yusuf S, Hawken S, Ounpuu S, et al.: Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004, 364:937–952.

    Article  PubMed  Google Scholar 

  14. Khuseyinova N, Koenig W: Apolipoprotein A-I and risk for cardiovascular diseases. Curr Atheroscler Rep 2006, 8:365–373.

    Article  PubMed  CAS  Google Scholar 

  15. Barter PJ, Rye KA: The rationale for using apo A-I as a clinical marker for cardiovascular risk. J Intern Med 2006, 259:447–454.

    Article  PubMed  CAS  Google Scholar 

  16. Lewis G: Determinants of plasma HDL concentrations and reverse cholesterol transport. Curr Opin Cardiol 2006, 21:345–352.

    Article  PubMed  Google Scholar 

  17. Tremblay AJ, Sniderman AD, Gagne C, et al.: Differential impact of plasma triglycerides on HDL-cholesterol and HDL-apo A-1 in a large cohort. Clin Biochem 2007, 40:25–29.

    Article  PubMed  CAS  Google Scholar 

  18. Nissen SE, Tsunoda T, Tuzcu EM, et al.: Effect of recombinant ApoA-1 Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 2003, 290:2292–2300.

    Article  PubMed  CAS  Google Scholar 

  19. Nicholls SJ, Dusting GJ, Cutri B, et al.: Reconstituted high-density lipoproteins inhibit the acute pro-oxidant and proinflammatory vascular changes induced by a periarterial collar in normocholesterolemic rabbits. Circulation 2005, 111:1543–1550.

    Article  PubMed  CAS  Google Scholar 

  20. Marcovina S, Packard CJ: Measurement and meaning of apolipoprotein AI and apolipoprotein B plasma levels. J Intern Med 2006, 259:437–446.

    Article  PubMed  CAS  Google Scholar 

  21. Sankatsing RR, Fouchier SW, de Haan S, et al.: Hepatic and cardiovascular consequences of familial hypobetalipoproteinemia. Arterioscler Thromb Vasc Biol 2005, 25:1979–1984.

    Article  PubMed  CAS  Google Scholar 

  22. Jansen AC, van Aalst-Cohen ES, Tanck MW, et al.: The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients. J Intern Med 2004, C

  23. Singaraja RR, Brunham LR, Visscher H, et al.: Efflux and atherosclerosis. The clinical and biocehmical impact of variations in the ABCA1 gene. Arterioscler Thromb Vasc Biol 2003, 23:1322–1332.

    Article  PubMed  CAS  Google Scholar 

  24. Hovingh GK, de Groot E, van der Steeg W, et al.: Inherited disorders of HDL metabolism and atherosclerosis. Curr Opin Lipidol 2007, 16:139–145.

    Article  Google Scholar 

  25. Attie AD, Kastelein JP, Hayden MR: Pivotal role of ABCA1 in reverse cholesterol transport influencing HDL levels and susceptibility to atherosclerosis. J Lipid Res 2001, 42:1717–1726.

    PubMed  CAS  Google Scholar 

  26. Miller M, Rhyne J, Hong SH, et al.: Do mutations causing low HDL-C promote increased carotid intima-media thickness? Clin Chim Acta 2007, 377:273–275.

    Article  PubMed  CAS  Google Scholar 

  27. Schaefer EJ, Heaton WH, Wetzel MG, Brewer HB Jr: Plasma apolipoprotein a-1 absence associated with a marked reduction of high density lipoproteins and premature coronary artery disease. Arterioscler Thromb Vasc Biol 1982, 2:16–26.

    CAS  Google Scholar 

  28. Genest J Jr, Bard JM, Fruchart JC, et al.: Familial hypoalphalipoproteinemia in premature coronary artery disease. Arterioscler Thromb Vasc Biol 1993, 13:1728–1737.

    Google Scholar 

  29. Hovingh GK, Brownlie A, Bisoendial RJ, et al.: A novel apoA-I mutation (L1789) leads to endothelial dysfunction, increased arterial wall thickness, and premature coronary artery disease. J Am Coll Cardiol 2004, 44:1429–1435.

    Article  PubMed  CAS  Google Scholar 

  30. Kuivenhoven JA, Pritchard H, Hill J, et al.: The molecular pathology of lecithin:cholesterol acyltransferase (LCAT). J Lipid Res 1997, 38:191–205.

    PubMed  CAS  Google Scholar 

  31. Singaraja RR, Visscher H, James ER, et al.: Specific mutations in ABCA1 have discrete effects on ABCA1 function and lipid phenotypes both in vivo and in vitro. Circ Res 2006, 99:389–397.

    Article  PubMed  CAS  Google Scholar 

  32. Kiss RS, Kavaslar N, Okuhira KI, et al.: Genetic etiology of isolated low HDL syndrome. Incidence and heterogeneity of efflux defects. Arterioscler Thromb Vasc Biol 2007, Feb 15:[Epub ahead of print].

  33. Sarov-Blat L, Kiss RS, Haidar B, et al.: Predominance of a proinflammatory phenotype in monocyte-derived macrophages from subjects with low plasma HDL-cholesterol. Arterioscler Thromb Vasc Biol 2007, 27:1115–1122.

    Article  PubMed  CAS  Google Scholar 

  34. Tall AR: The failure of torcetrapib: was it the molecule or the mechanism? Arterioscler Thromb Vasc Biol 2007, 27:257–260.

    Article  PubMed  CAS  Google Scholar 

  35. Rader DJ, Ikewaki K, Duverger N, et al.: Very low high-density lipoproteins without coronary atherosclerosis. Lancet 1993, 342:1455–1458.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Allan D. Sniderman MD.

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Sniderman, A.D., Kiss, R.S. The strengths and limitations of the ApoB/ApoA-I ratio to predict the risk of vascular disease: a hegelian analysis. Curr Atheroscler Rep 9, 261–265 (2007). https://doi.org/10.1007/s11883-007-0031-6

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