Journal of Clinical Lipidology
Volume 1, Issue 6 , Pages 583-592 , December 2007

LDL particle number and risk of future cardiovascular disease in the Framingham Offspring Study—Implications for LDL management

  • William C. Cromwell, MD

      Affiliations

    • Division of Lipoprotein Disorders, Presbyterian Center for Preventive Cardiology, 125 Baldwin Avenue, Suite 200, Charlotte, NC 28204, USA
    • Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA
    • Corresponding Author InformationCorresponding author.
    • ,
  • James D. Otvos, PhD

      Affiliations

    • LipoScience, Inc., Raleigh, NC, USA
    • ,
  • Michelle J. Keyes, PhD

      Affiliations

    • The Framingham Study, Boston University School of Medicine, Framingham, MA, USA
    • Department of Mathematics and Statistics, Boston University, Boston, MA
    • ,
  • Michael J. Pencina, PhD

      Affiliations

    • Department of Mathematics and Statistics, Boston University, Boston, MA
    • ,
  • Lisa Sullivan, PhD

      Affiliations

    • Department of Biostatistics, Boston University, Boston, MA
    • ,
  • Ramachandran S. Vasan, MD

      Affiliations

    • The Framingham Study, Boston University School of Medicine, Framingham, MA, USA
    • Department of Preventive Medicine, Cardiology Section, Boston University, Boston, MA
    • ,
  • Peter W.F. Wilson, MD

      Affiliations

    • Cardiology Division, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
    • ,
  • Ralph B. D’Agostino, PhD

      Affiliations

    • The Framingham Study, Boston University School of Medicine, Framingham, MA, USA
    • Department of Mathematics and Statistics, Boston University, Boston, MA

Received 19 June 2007 ,Accepted 11 October 2007.

References 

  1. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502
  2. Sniderman A, Vu H, Cianflone K. Effect of moderate hypertriglyceridemia on the relation of plasma total and LDL apoB levels. Atherosclerosis. 1991;89:109–116
  3. Jeyarajah EJ, Cromwell WC, Otvos JD. Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy. Clin Lab Med. 2006;26:847–870
  4. Executive Summary of The 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). JAMA. 2001;285:2486–2497
  5. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227–239
  6. Otvos JD, Jeyarajah EJ, Cromwell WC. Measurement issues related to lipoprotein heterogeneity. Am J Cardiol. 2002;90(suppl):22i–29i
  7. Cromwell WC, Otvos JD. Low-density lipoprotein particle number and risk for cardiovascular disease. Curr Atheroscler Rep. 2004;6:381–387
  8. Sniderman AD, Furberg CD, Keech A, et al. Apolipoproteins versus lipids as indices of coronary risk and as targets for statin therapy treatment. Lancet. 2003;361:777–780
  9. Sniderman AD, St-Pierre AC, Cantin B, Dagenais GR, Despres J-P, Lamarche B. Concordance/discordance between plasma apolipoprotein B levels and the cholesterol indexes of atherosclerotic risk. Am J Cardiol. 2003;91:1173–1177
  10. Kim BJ, Hwang ST, Sung KC, et al. Comparison of the relationships between serum apolipoprotein B and serum lipid distributions. Clin Chem. 2005;51:2257–2263
  11. Stein EA, Sniderman A, Laskarzewski P. Assessment of reaching goal in patients with combined hyperlipidemia: low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, or apolipoprotein B. Am J Cardiol. 2005;96(suppl):36K–43K
  12. 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
  13. Cromwell WC, Otvos JD. Heterogeneity of low density lipoprotein particle number in patients with type 2 diabetes mellitus and low density lipoprotein cholesterol <100 mg/dl. Am J Cardiol. 2006;98:1599–1602
  14. 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
  15. Grundy SM. Low-density lipoprotein, non-high-density lipoprotein, and apolipoprotein B as targets of lipid-lowering therapy. Circulation. 2002;106:2526–2529
  16. Liu J, Sempos CT, Donahue RP, Dorn J, Trevisan M, Grundy SM. Non–high-density lipoprotein and very-low-density lipoprotein cholesterol and their risk predictive values in coronary heart disease. Am J Cardiol. 2006;98:1363–1368
  17. Kannel WB, Feinleib M, McNamara PM, Garrison RJ, Castelli WP. An investigation of coronary heart disease in families (The Framingham offspring study). Am J Epidemiol. 1979;110:281–290
  18. McNamara JR, Schaefer EJ. Automated enzymatic standardized lipid analyses for plasma and lipoprotein fractions. Clin Chim Acta. 1987;166:1–8
  19. Freedman DS, Otvos JD, Jeyarajah EJ, et al. Sex and age differences in lipoprotein subclasses measured by nuclear magnetic resonance spectroscopy: The Framingham Study. Clin Chem. 2004;50:1189–1200
  20. McNamara JR, Small DM, Li Z, Schaefer EJ. Differences in LDL subspecies involve alterations in lipid composition and conformational changes in apolipoprotein B. J Lipid Res. 1996;37:1924–1935
  21. Some risk factors related to the annual incidence of cardiovascular disease and death in pooled repeated biennial measurements. Framingham Heart Study: 30 Year Follow-Up. Bethesda, MD: US Department of Health and Human Services; 1987;
  22. Harvengt C, Heller FR, Martiat P, Van Nieuwenhuyze Y. Short-term effects of beta blockers atenolol, nadolol, pindolol, and propranolol on lipoprotein metabolism in normolipemic subjects. J Clin Pharmacol. 1987;27:475–480
  23. Festa A, Williams K, Hanley AJG, et al. Nuclear magnetic resonance lipoprotein abnormalities in prediabetic subjects in the Insulin Resistance Atherosclerosis Study (IRAS). Circulation. 2005;111:3465–3472
  24. Kuller LH, Arnold A, Tracy R, et al. Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol. 2002;22:1175–1180
  25. Rosenson RS, Otvos JD, Freedman DS. Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC-I) Trial. Am J Cardiol. 2002;90:89–94
  26. Blake GJ, Otvos JD, Rifai N, Ridker PM. Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women. Circulation. 2002;106:1930–1937
  27. Otvos JD, Collins D, Freedman DS, et al. LDL and HDL particle subclasses predict coronary events and are changed favorably by gemfibrozil therapy in the Veterans Affairs HDL Intervention Trial (VA-HIT). Circulation. 2006;113:1556–1563
  28. Hayward RA, Hofer TP, Sandeep V. Lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem. Ann Intern Med. 2006;145:520–530
  29. Davidson MH. Reducing residual risk for patients on statin therapy: the potential role of combination therapy. Am J Cardiol. 2005;96(suppl):3K–13K
  30. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet. 2002;360:7–22
  31. Deedwania P, Barter P, Carmena R, et al. Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study. Lancet. 2006;368:919–928
  32. Berneis KK, Krauss RM. Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res. 2002;43:1363–1379
  33. Barter PJ, Brewer HB, Chapman MJ, Hennekens CH, Rader DJ, Tall AR. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol. 2003;23:160–167
  34. Guerin M, Lassel TS, Le Goff W, Farnier MA, Chapman MJ. Action of atorvastatin in combined hyperlipidemia: preferential reduction of cholesterol ester transfer from HDL to VLDL1 particles. Arterioscler Thromb Vasc Biol. 2000;20:189–197
  35. Miller M, Dolinar C, Cromwell W, Otvos JD. Effectiveness of high doses of simvastatin as monotherapy in mixed hyperlipidemia. Am J Cardiol. 2001;87:232–234
  36. Rosenson RS, Shalaurova I, Freedman DS, Otvos JD. Effects of pravastatin treatment on lipoprotein subclass profiles and particle size in the PLAC-I Trial. Atherosclerosis. 2002;160:41–48
  37. Blake GJ, Albert MA, Rifai N, Ridker PM. Effect of pravastatin on LDL particle concentration as determined by NMR spectroscopy: a substudy of a randomized placebo controlled trial. Eur Heart J. 2003;24:1843–1847
  38. Soedamah SS, Colhoun HM, Thomason MJ, et al. The effect of atorvastatin on serum lipids, lipoproteins and NMR spectroscopy defined lipoprotein subclasses in type 2 diabetic patients with ischemic heart disease. Atherosclerosis. 2003;167:243–255
  39. 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

PII: S1933-2874(07)00283-8

doi: 10.1016/j.jacl.2007.10.001

Journal of Clinical Lipidology
Volume 1, Issue 6 , Pages 583-592 , December 2007

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