Skip to main content
PMC home page
Clinical Cardiology logoLink to Clinical Cardiology
. 2009 Sep 9;32(9):482–486. doi: 10.1002/clc.20559

Apolipoprotein Measurements: Is More Widespread Use Clinically Indicated?

Michael H Davidson 1,✉
PMCID: PMC6653425  PMID: 19743499

Abstract

Apolipoprotein (apo) B may be a more sensitive measure of atherogenicity than low‐density lipoprotein cholesterol (LDL‐C) and a better index for assessing cardiovascular risk. The refined risk assessment provided by apo B may be important in patients at high cardiometabolic risk such as those with diabetes mellitus or metabolic syndrome, as these conditions are often associated with normal LDL‐C values but increased numbers of small, dense low‐density lipoprotein (LDL) particles (indicating increased levels of apo B). Although apo B is not currently a treatment target in the United States cholesterol‐lowering guidelines, a consensus conference endorsed by the American Diabetes Association and the American College of Cardiology recently recommended that apo B be added as a therapeutic target in patients at high cardiometabolic risk and in patients with clinical cardiovascular disease or diabetes. Suggested target goals are < 90 for high risk and < 80 mg/dL for highest risk patients. Current clinical data indicate that intensive statin therapy can lower apo B to meet this aggressive goal. While the proatherogenic/antiatherogenic ratio of apo B/apo A‐I is a better risk discriminator than the single proatherogenic measurement (apo B), clinical trial data are lacking regarding the impact of increasing apo A‐I and high‐density lipoprotein on outcomes. Copyright © 2009 Wiley Periodicals, Inc.

Full Text

The Full Text of this article is available as a PDF (117.8 KB).

References

  • 1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): final report. Circulation 2002; 106: 3143–3421. [PubMed] [Google Scholar]
  • 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: 247–258. [DOI] [PubMed] [Google Scholar]
  • 3. Marcovina S, Packard CJ. Measurement and meaning of apolipoprotein AI and apolipoprotein B plasma levels. J Intern Med 2006; 259: 437–446. [DOI] [PubMed] [Google Scholar]
  • 4. Walldius G, Jungner I. The apoB/apoA‐I 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. [DOI] [PubMed] [Google Scholar]
  • 5. Grundy SM. Low‐density lipoprotein, nonhigh‐density lipoprotein, and apolipoprotein B as targets of lipid‐lowering therapy. Circulation 2002; 106: 2526–2529. [DOI] [PubMed] [Google Scholar]
  • 6. Rader DJ. Molecular regulation of HDL metabolism and function: implications for novel therapies. J Clin Invest 2006; 116: 3090–3100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Bachorik PS, Lovejoy KL, Carroll MD, Johnson CL. Apolipoprotein B and AI distributions in the United States, 1988–1991: results of the National Health and Nutrition Examination Survey III (NHANES III). Clin Chem 1997; 43: 2364–2378. [PubMed] [Google Scholar]
  • 8. Contois JH, McNamara JR, Lammi‐Keefe CJ, Wilson PWF, Massov T, Schaefer EJ. Reference intervals for plasma apolipoprotein A‐I determined with a standardized commercial immunoturbidimetric assay: results from the Framingham Offspring Study. Clin Chem 1996; 42: 507–514. [PubMed] [Google Scholar]
  • 9. Contois JH, McNamara JR, Lammi‐Keefe CJ, Wilson PWF, Massov T, Schaefer EJ: Reference intervals for plasma apolipoprotein B determined with a standardized commercial immunoturbidimetric assay: results from the Framingham Offspring Study. Clin Chem 1996; 42: 515–523. [PubMed] [Google Scholar]
  • 10. Marcovina SM, Albers JJ, Kennedy H, Mei JV, Henderson LO, Harnnon WH. International federation of clinical chemistry standardization project for measurements of apolipoprotein A‐1 and B: IV. Comparability of apolipoprotein B values by use of international reference material. Clin Chem 1994; 40: 586–592. [PubMed] [Google Scholar]
  • 11. Genest J, Frohlich J, Fodor G, McPherson R (the Working Group on Hypercholesterolemia and Other Dyslipidemias): Recommendations for the management of dyslipidemia and the prevention of cardiovascular disease: summary of the 2003 update. CMAJ 2003; 169: 921–924. [PMC free article] [PubMed] [Google Scholar]
  • 12. Brunzell JD, Davidson M, Furberg CD, et al. Lipoprotein management in patients with cardiometabolic risk: Consensus Conference Report from the American Diabetes Association and the American College of Cardiology Foundation. J Am Coll Cardiol 2008; 51: 1512–1524. [DOI] [PubMed] [Google Scholar]
  • 13. Kathiresan S, Otvos JD, Sullivan LM, et al. Increased small low‐density lipoprotein particle number: a prominent feature of the metabolic syndrome in the Framingham Heart Study. Circulation 2006; 113: 20–29. [DOI] [PubMed] [Google Scholar]
  • 14. Lamarche B, Moorjani S, Lupien PJ, et al. Apolipoprotein A‐I and B levels and the risk of ischemic heart disease during a five‐year follow‐up of men in the Quebec Cardiovascular Study. Circulation 1996; 94: 273–278. [DOI] [PubMed] [Google Scholar]
  • 15. St‐Pierre AC, Cantin B, Dagenais GR, et al. Low‐density lipoprotein subfractions and the long‐term risk of ischemic heart disease in men: 13‐year follow‐up data from the Québec Cardiovascular Study. Arterioscler Thromb Vasc Biol 2005; 25: 553–559. [DOI] [PubMed] [Google Scholar]
  • 16. St‐Pierre AC, Cantin B, Dagenais GR, Després J‐P, Lamarche B. Apolipoprotein‐B, low‐density lipoprotein cholesterol, and the long‐term risk of coronary heart disease in men. Am J Cardiol 2006; 97: 997–1001. [DOI] [PubMed] [Google Scholar]
  • 17. Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E. High apolipoprotein B, low apolipoprotein A‐I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet 2001; 358: 2026–2033. [DOI] [PubMed] [Google Scholar]
  • 18. Williams K, Sniderman AD, Sattar N, D'Agostino R Jr, Wagenknecht LE, Haffner SM. Comparison of the associations of apolipoprotein B and low‐density lipoprotein cholesterol with other cardiovascular risk factors in the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 2003; 108: 2312–2316. [DOI] [PubMed] [Google Scholar]
  • 19. Corsetti JP, Zareba W, Moss AJ, Sparks CE. Apolipoprotein B determines risk for recurrent coronary events in postinfarction patients with metabolic syndrome. Atherosclerosis 2004; 177: 367–373. [DOI] [PubMed] [Google Scholar]
  • 20. Gotto AM Jr, 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. [DOI] [PubMed] [Google Scholar]
  • 21. Sacks FM, Alaupovic P, Moye LA, et al. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) Trial. Circulation 2000; 102: 1886–1892. [DOI] [PubMed] [Google Scholar]
  • 22. Simes RJ, Marschner IC, Hunt D, et al; on behalf of the LIPID Study Investigators. Relationship between lipid levels and clinical outcomes in the Long‐Term Intervention With Pravastatin in 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. [DOI] [PubMed] [Google Scholar]
  • 23. Kastelein JJP, van der Steeg WA, Holme I, et al; for the TNT and IDEAL Study Groups. Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment. Circulation 2008; 117: 3002–3009. [DOI] [PubMed] [Google Scholar]
  • 24. Brown G, Alberts JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid‐lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990; 323: 1289–1298. [DOI] [PubMed] [Google Scholar]
  • 25. Meisinger C, Loewel H, Mraz W, Koenig W. Prognostic value of apolipoprotein B and A‐I in the prediction of myocardial infarction in middle‐aged men and women: results from the MONICA/KORA Augsburg cohort study. Eur Heart J 2005; 26: 271–278. [DOI] [PubMed] [Google Scholar]
  • 26. Sharrett AR, Ballantyne CM, Coady SA, et al. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A‐I and B, and HDL density subfractions: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 2001; 104: 1108–1113. [DOI] [PubMed] [Google Scholar]
  • 27. Luc G, Bard J‐M, Ferrières J, et al; on behalf of the PRIME Study Group. Value of HDL cholesterol, apolipoprotein A‐I, lipoprotein A‐I, and lipoprotein A‐I/A‐II in prediction of coronary heart disease: the PRIME Study. Arterioscler Thromb Vasc Biol 2002; 22: 1155–1161. [DOI] [PubMed] [Google Scholar]
  • 28. van der Steeg WA, Boekholdt SM, Stein EA, et al. Role of the apolipoprotein B‐apolipoprotein A‐I ratio in cardiovascular risk assessment: a case‐control analysis in EPIC‐Norfolk. Ann Intern Med 2007; 146: 640–648. [DOI] [PubMed] [Google Scholar]
  • 29. 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: 776–785. [DOI] [PubMed] [Google Scholar]
  • 30. Yusuf S, Hawken S, Ôunpuu S, et al; on behalf of the INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case‐control study. Lancet 2004; 364: 937–952. [DOI] [PubMed] [Google Scholar]
  • 31. Ooi EMM, Barrett PHR, Chan DC, Nestel PJ, Watts GF. Dose‐dependent effect of rosuvastatin on apolipoprotein B‐100 kinetics in the metabolic syndrome. Atherosclerosis 2008; 197: 139–146. [DOI] [PubMed] [Google Scholar]
  • 32. Caslake MJ, Stewart G, Day SP, et al. Phenotype‐dependent and ‐independent actions of rosuvastatin on atherogenic lipoprotein subfractions in hyperlipidaemia. Atherosclerosis 2003; 171: 245–253. [DOI] [PubMed] [Google Scholar]
  • 33. Ballantyne CM, Blazing MA, Hunninghake DB, et al: Effect on high‐density lipoprotein cholesterol of maximum dose simvastatin and atorvastatin in patients with hypercholesterolemia: results of the Comparative HDL Efficacy and Safety Study (CHESS). Am Heart J 2003; 146: 862–869. [DOI] [PubMed] [Google Scholar]
  • 34. Jones PH, Hunninghake DB, Ferdinand KC, et al; for the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) Study Group. Effects of rosuvastatin versus atorvastatin, simvastatin, and pravastatin on non‐high‐density lipoprotein cholesterol, apolipoproteins, and lipid ratios in patients with hypercholesterolemia: additional results from the STELLAR trial. Clin Ther 2004; 26: 1388–1399. [DOI] [PubMed] [Google Scholar]
  • 35. Lamon‐Fava S, Diffenderfer MR, Barrett PHR, et al. Effects of different doses of atorvastatin on human apolipoprotein B‐100, B‐48, and A‐I metabolism. J Lipid Res 2007; 48: 1746–1753. [DOI] [PubMed] [Google Scholar]
  • 36. Betteridge DJ, Gibson JM; on behalf of the ANDROMEDA Study Investigators. Effects of rosuvastatin on lipids, lipoproteins and apolipoproteins in the dyslipidaemia of diabetes. Diabet Med 2007; 24(5): 541–549. [DOI] [PubMed] [Google Scholar]

Articles from Clinical Cardiology are provided here courtesy of Wiley

RESOURCES