Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2011

Open Access 01-12-2011 | Original investigation

Non-HDL-cholesterol as valid surrogate to apolipoprotein B100 measurement in diabetes: Discriminant Ratio and unbiased equivalence

Authors: Michel P Hermans, Frank M Sacks, Sylvie A Ahn, Michel F Rousseau

Published in: Cardiovascular Diabetology | Issue 1/2011

Login to get access

Abstract

Background

Apolipoprotein B100 (apoB) is a superior indicator of CV risk than total or LDL-C. Non-HDL-C represents a simple surrogate for apoB in hypertriglyceridemic and/or T2DM patients. ApoB and non-HDL-C show high correlation, although the degree of mutual concordance remains debated in CV risk evaluation.

Objectives

We used the Discriminant Ratio (DR) methodology to compare the performance of non-HDL-C with that of apoB to rank diabetic patients according to dyslipidemia and to establish the underlying relationship between these variables taking measurement noise and intra-/intersubject variation into account, and to derive an unbiased equivalence equation.

Methods

Fasting total C, HDL-C, apoB and triglycerides were measured in 45 diabetic patients. The DR of the underlying between-subject standard deviation (SD) to the within-subject SD was calculated from duplicates. Correlation coefficients between pairs were adjusted to include an estimate of the underlying correlation.

Results

Mean values [day 1 (1SD)] were 143 (36) mg/dl (non-HDL-C) and 98 (24) mg/dl (apoB). The DR's of both parameters were similar (1.76 and 1.83) (p = 0.83). Pearson's product-moment correlation coefficient between tests was very high (0.94), reaching unity (1.00) after attenuation adjustment. The unbiased equation of equivalence relating apoB to non-HDL-C had a slope of 0.65 and an intercept of 6.3 mg/dl.

Conclusions

The discrimination power of non-HDL-C is similar to that of apoB to rank diabetic patients according to atherogenic cholesterol and lipoprotein burden. Since true correlation between variables reached unity, non-HDL-C may provide not only a metabolic surrogate but also a candidate biometrical equivalent to apoB, as non-HDL-C calculation is readily available.
Appendix
Available only for authorised users
Literature
1.
go back to reference Atlas of Atherosclerosis: Risk Factors and Treatment. Edited by: Peter W Wilson. 2003, Springer-Verlag New York, 284. Atlas of Atherosclerosis: Risk Factors and Treatment. Edited by: Peter W Wilson. 2003, Springer-Verlag New York, 284.
2.
go back to reference 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: 3143-221. 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: 3143-221.
3.
go back to reference Sniderman AD, St-Pierre AC, Cantin B, Dagenais GR, Després JP, Lamarche B: Concordance/discordance between plasma apolipoprotein B levels and the cholesterol indexes of atherosclerotic risk. Am J Cardiol. 2003, 91: 1173-7. 10.1016/S0002-9149(03)00262-5.CrossRefPubMed Sniderman AD, St-Pierre AC, Cantin B, Dagenais GR, Després JP, Lamarche B: Concordance/discordance between plasma apolipoprotein B levels and the cholesterol indexes of atherosclerotic risk. Am J Cardiol. 2003, 91: 1173-7. 10.1016/S0002-9149(03)00262-5.CrossRefPubMed
4.
go back to reference Wägner AM, Pérez A, Zapico E, Ordóñez-Llanos J: Non-HDL cholesterol and apolipoprotein B in the dyslipidemic classification of type 2 diabetic patients. Diabetes Care. 2003, 26: 2048-51.CrossRefPubMed Wägner AM, Pérez A, Zapico E, Ordóñez-Llanos J: Non-HDL cholesterol and apolipoprotein B in the dyslipidemic classification of type 2 diabetic patients. Diabetes Care. 2003, 26: 2048-51.CrossRefPubMed
5.
go back to reference Sniderman AD: Non-HDL cholesterol versus apolipoprotein B in diabetic dyslipoproteinemia. Alternatives and surrogates versus the real thing. Diabetes Care. 2003, 26: 2207-8. 10.2337/diacare.26.7.2207.CrossRefPubMed Sniderman AD: Non-HDL cholesterol versus apolipoprotein B in diabetic dyslipoproteinemia. Alternatives and surrogates versus the real thing. Diabetes Care. 2003, 26: 2207-8. 10.2337/diacare.26.7.2207.CrossRefPubMed
6.
go back to reference Lu W, Resnick HE, Jablonski KA, Jones KL, Jain AK, Howard WJ, Robbins DC, Howard BV: Non-HDL cholesterol as a predictor of cardiovascular disease in type 2 diabetes : The Strong Heart Study. Diab Care. 2003, 26: 16-23. 10.2337/diacare.26.1.16.CrossRef Lu W, Resnick HE, Jablonski KA, Jones KL, Jain AK, Howard WJ, Robbins DC, Howard BV: Non-HDL cholesterol as a predictor of cardiovascular disease in type 2 diabetes : The Strong Heart Study. Diab Care. 2003, 26: 16-23. 10.2337/diacare.26.1.16.CrossRef
7.
go back to reference Sniderman AD: Apolipoprotein B versus non-high-density lipoprotein cholesterol. And the winner is... Circulation. 2005, 112: 3366-7. 10.1161/CIRCULATIONAHA.105.583336.CrossRefPubMed Sniderman AD: Apolipoprotein B versus non-high-density lipoprotein cholesterol. And the winner is... Circulation. 2005, 112: 3366-7. 10.1161/CIRCULATIONAHA.105.583336.CrossRefPubMed
8.
go back to reference Pischon T, Girman GJ, Sacks FM, Rifai N, Stampfer NJ, Rimm EB: Non-high-density lipoprotein cholesterol and Apolipoprotein B in the prediction of coronary heart disease in men, Circulation. 2005, 112: 3375-83. Pischon T, Girman GJ, Sacks FM, Rifai N, Stampfer NJ, Rimm EB: Non-high-density lipoprotein cholesterol and Apolipoprotein B in the prediction of coronary heart disease in men, Circulation. 2005, 112: 3375-83.
9.
go back to reference Denke MA: Weighing in before the fight. Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol versus Apolipoprotein B as the best predictor for coronary heart disease and the best measure of therapy. Circulation. 2005, 112: 3368-70. 10.1161/CIRCULATIONAHA.105.588178.CrossRefPubMed Denke MA: Weighing in before the fight. Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol versus Apolipoprotein B as the best predictor for coronary heart disease and the best measure of therapy. Circulation. 2005, 112: 3368-70. 10.1161/CIRCULATIONAHA.105.588178.CrossRefPubMed
10.
go back to reference Holman RR, Coleman RL, Shine S, Stevens RJ: Non-HDL cholesterol is less informative than the total-to-HDL cholesterol ratio in predicting cardiovascular risk in type 2 diabetes. Diab Care. 2005, 28: 1796-7. 10.2337/diacare.28.7.1796.CrossRef Holman RR, Coleman RL, Shine S, Stevens RJ: Non-HDL cholesterol is less informative than the total-to-HDL cholesterol ratio in predicting cardiovascular risk in type 2 diabetes. Diab Care. 2005, 28: 1796-7. 10.2337/diacare.28.7.1796.CrossRef
11.
go back to reference Levinson SS: Comparison of apolipoprotein B and non-high-density lipoprotein cholesterol for identifying coronary artery disease risk based on receiver operating curve analysis. Am J Clin Pathol. 2007, 127: 449-55. 10.1309/22M22RF48PX9UT9T.CrossRefPubMed Levinson SS: Comparison of apolipoprotein B and non-high-density lipoprotein cholesterol for identifying coronary artery disease risk based on receiver operating curve analysis. Am J Clin Pathol. 2007, 127: 449-55. 10.1309/22M22RF48PX9UT9T.CrossRefPubMed
12.
go back to reference 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: 2026-33. 10.1016/S0140-6736(01)07098-2.CrossRefPubMed 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: 2026-33. 10.1016/S0140-6736(01)07098-2.CrossRefPubMed
13.
go back to reference Yusuf S, Hawken S, Ôunpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L, 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: 937-52. 10.1016/S0140-6736(04)17018-9.CrossRefPubMed Yusuf S, Hawken S, Ôunpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L, 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: 937-52. 10.1016/S0140-6736(04)17018-9.CrossRefPubMed
14.
go back to reference Hermans MP, Ahn SA, Rousseau MF: The non-HDL-C/HDL-C ratio provides cardiovascular risk stratification similar to the ApoB/ApoA1 ratio in diabetics: Comparison with reference lipid markers Diabetes & Metabolic Syndrome. Clin Res & Rev. 2007, 1: 23-8.CrossRef Hermans MP, Ahn SA, Rousseau MF: The non-HDL-C/HDL-C ratio provides cardiovascular risk stratification similar to the ApoB/ApoA1 ratio in diabetics: Comparison with reference lipid markers Diabetes & Metabolic Syndrome. Clin Res & Rev. 2007, 1: 23-8.CrossRef
15.
go back to reference Sierra-Johnson J, Fisher RM, Romero-Corral A, Somers VK, Lopez-Jimenez F, Ohrvik J, Walldius G, Hellenius ML, Hamsten A: Concentration of apolipoprotein B is comparable with the apolipoprotein B/apolipoprotein A-I ratio and better than routine clinical lipid measurements in predicting coronary heart disease mortality: findings from a multi-ethnic US population. Eur Heart J. 2009, 30: 710-7. 10.1093/eurheartj/ehn347.PubMedCentralCrossRefPubMed Sierra-Johnson J, Fisher RM, Romero-Corral A, Somers VK, Lopez-Jimenez F, Ohrvik J, Walldius G, Hellenius ML, Hamsten A: Concentration of apolipoprotein B is comparable with the apolipoprotein B/apolipoprotein A-I ratio and better than routine clinical lipid measurements in predicting coronary heart disease mortality: findings from a multi-ethnic US population. Eur Heart J. 2009, 30: 710-7. 10.1093/eurheartj/ehn347.PubMedCentralCrossRefPubMed
16.
go back to reference Garvey WT, Kwon S, Zheng D, Shaughnessy S, Wallace P, Hutto A, Pugh K, Jenkins AJ, Klein RL, Liao Y: Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes. 2003, 52: 453-62. 10.2337/diabetes.52.2.453.CrossRefPubMed Garvey WT, Kwon S, Zheng D, Shaughnessy S, Wallace P, Hutto A, Pugh K, Jenkins AJ, Klein RL, Liao Y: Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes. 2003, 52: 453-62. 10.2337/diabetes.52.2.453.CrossRefPubMed
17.
go back to reference Kathiresan S, Otvos JD, Sullivan LM, Keyes MJ, Schaefer EJ, Wilson PW, D'Agostino RB, Vasan RS, Robins SJ: Increased small low-density lipoprotein particle number. A prominent feature of the metabolic syndrome in the Framingham Heart Study. Circulation. 2006, 113: 20-9. 10.1161/CIRCULATIONAHA.105.567107.CrossRefPubMed Kathiresan S, Otvos JD, Sullivan LM, Keyes MJ, Schaefer EJ, Wilson PW, D'Agostino RB, Vasan RS, Robins SJ: Increased small low-density lipoprotein particle number. A prominent feature of the metabolic syndrome in the Framingham Heart Study. Circulation. 2006, 113: 20-9. 10.1161/CIRCULATIONAHA.105.567107.CrossRefPubMed
18.
go back to reference Brunzell JD, Davidson M, Furberg CD, Goldberg RB, Howard BV, Stein JH, Witztum JL, American Diabetes Association; American College of Cardiology Foundation: Lipoprotein management in patients with cardiometabolic risk. Consensus statement from the American Diabetes Association and the American College of Cardiology Foundation. Diabetes Care. 2008, 31: 811-22. 10.2337/dc08-9018.CrossRefPubMed Brunzell JD, Davidson M, Furberg CD, Goldberg RB, Howard BV, Stein JH, Witztum JL, American Diabetes Association; American College of Cardiology Foundation: Lipoprotein management in patients with cardiometabolic risk. Consensus statement from the American Diabetes Association and the American College of Cardiology Foundation. Diabetes Care. 2008, 31: 811-22. 10.2337/dc08-9018.CrossRefPubMed
19.
go back to reference Levy JC, Morris RJ, Hammersley M, Turner RC: Discrimination, adjusted correlation, and equivalence of imprecise tests: application to glucose tolerance. Am J Physiol. 1999, 276: E365-75.PubMed Levy JC, Morris RJ, Hammersley M, Turner RC: Discrimination, adjusted correlation, and equivalence of imprecise tests: application to glucose tolerance. Am J Physiol. 1999, 276: E365-75.PubMed
20.
go back to reference Hermans MP, Levy JC, Morris RJ, Turner RC: Comparison of tests of beta-cell function across a range of glucose tolerance from normal to diabetes. Diabetes. 1999, 48: 1779-86. 10.2337/diabetes.48.9.1779.CrossRefPubMed Hermans MP, Levy JC, Morris RJ, Turner RC: Comparison of tests of beta-cell function across a range of glucose tolerance from normal to diabetes. Diabetes. 1999, 48: 1779-86. 10.2337/diabetes.48.9.1779.CrossRefPubMed
21.
go back to reference Hermans MP, Levy JC, Morris RJ, Turner RC: Comparison of insulin sensitivity tests across a range of glucose tolerance form normal to diabetes. Diabetologia. 1999, 42: 678-87. 10.1007/s001250051215.CrossRefPubMed Hermans MP, Levy JC, Morris RJ, Turner RC: Comparison of insulin sensitivity tests across a range of glucose tolerance form normal to diabetes. Diabetologia. 1999, 42: 678-87. 10.1007/s001250051215.CrossRefPubMed
22.
go back to reference 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.PubMed 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.PubMed
23.
go back to reference Lee SJ, Campos H, Moye LA, Sacks FM: LDL particles containing apolipoprotein CIII are independent risk factors for coronary events in diabetic patients. Arterioscl Thromb Vasc Biol. 2003, 23: 853-8. 10.1161/01.ATV.0000066131.01313.EB.CrossRefPubMed Lee SJ, Campos H, Moye LA, Sacks FM: LDL particles containing apolipoprotein CIII are independent risk factors for coronary events in diabetic patients. Arterioscl Thromb Vasc Biol. 2003, 23: 853-8. 10.1161/01.ATV.0000066131.01313.EB.CrossRefPubMed
24.
go back to reference Zheng CY, Khoo C, Ikewaki K, Sacks FM: Rapid turnover of apolipoprotein CIII containing triglyceride-rich lipoproteins contributing to formation of LDL subfractions. J Lipid Res. 2007, 48: 1190-203. 10.1194/jlr.P600011-JLR200.CrossRefPubMed Zheng CY, Khoo C, Ikewaki K, Sacks FM: Rapid turnover of apolipoprotein CIII containing triglyceride-rich lipoproteins contributing to formation of LDL subfractions. J Lipid Res. 2007, 48: 1190-203. 10.1194/jlr.P600011-JLR200.CrossRefPubMed
25.
go back to reference Kawakami A, Aikawa M, Libby P, Alcaide P, Luscinskas FW, Sacks FM: Apolipoprotein CIII in apoB lipoproteins enhances the adhesion of human monocytic cells to endothelial cells. Circulation. 2006, 113: 691-700. 10.1161/CIRCULATIONAHA.105.591743.CrossRefPubMed Kawakami A, Aikawa M, Libby P, Alcaide P, Luscinskas FW, Sacks FM: Apolipoprotein CIII in apoB lipoproteins enhances the adhesion of human monocytic cells to endothelial cells. Circulation. 2006, 113: 691-700. 10.1161/CIRCULATIONAHA.105.591743.CrossRefPubMed
26.
go back to reference Genest J, McPherson R, Frohlich J, Anderson T, Campbell N, Carpentier A, Couture P, Dufour R, Fodor G, Francis GA, Grover S, Gupta M, Hegele RA, Lau DC, Leiter L, Lewis GF, Lonn E, Mancini GB, Ng D, Pearson GJ, Sniderman A, Stone JA, Ur E: Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult - 2009 recommendations. Can J Cardiol. 2009, 25: 567-79. 2009PubMedCentralCrossRefPubMed Genest J, McPherson R, Frohlich J, Anderson T, Campbell N, Carpentier A, Couture P, Dufour R, Fodor G, Francis GA, Grover S, Gupta M, Hegele RA, Lau DC, Leiter L, Lewis GF, Lonn E, Mancini GB, Ng D, Pearson GJ, Sniderman A, Stone JA, Ur E: Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult - 2009 recommendations. Can J Cardiol. 2009, 25: 567-79. 2009PubMedCentralCrossRefPubMed
27.
go back to reference Hermans MP, Fruchart JC: Reducing residual vascular risk in patients with atherogenic dyslipidaemia: where do we go from here?. Clinical Lipidology Review. 2010, 5: 811-26. 10.2217/clp.10.65.CrossRef Hermans MP, Fruchart JC: Reducing residual vascular risk in patients with atherogenic dyslipidaemia: where do we go from here?. Clinical Lipidology Review. 2010, 5: 811-26. 10.2217/clp.10.65.CrossRef
28.
go back to reference Hermans MP, Ahn SA, Rousseau MF: Log(TG)/HDL-C is related to both residual cardiometabolic risk and β-cell function loss in type 2 diabetes males. Cardiovascular Diabetology. 2010, 9: 88-10.1186/1475-2840-9-88.PubMedCentralCrossRefPubMed Hermans MP, Ahn SA, Rousseau MF: Log(TG)/HDL-C is related to both residual cardiometabolic risk and β-cell function loss in type 2 diabetes males. Cardiovascular Diabetology. 2010, 9: 88-10.1186/1475-2840-9-88.PubMedCentralCrossRefPubMed
Metadata
Title
Non-HDL-cholesterol as valid surrogate to apolipoprotein B100 measurement in diabetes: Discriminant Ratio and unbiased equivalence
Authors
Michel P Hermans
Frank M Sacks
Sylvie A Ahn
Michel F Rousseau
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2011
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-10-20

Other articles of this Issue 1/2011

Cardiovascular Diabetology 1/2011 Go to the issue