Skip to main content
Erschienen in: Diabetologia 2/2009

01.02.2009 | Article

Apolipoproteins, cardiovascular risk and statin response in type 2 diabetes: the Collaborative Atorvastatin Diabetes Study (CARDS)

verfasst von: V. Charlton-Menys, D. J. Betteridge, H. Colhoun, J. Fuller, M. France, G. A. Hitman, S. J. Livingstone, H. A. W. Neil, C. B. Newman, M. Szarek, D. A. DeMicco, P. N. Durrington

Erschienen in: Diabetologia | Ausgabe 2/2009

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

Controversy surrounds whether the ratio of apolipoprotein B (ApoB) to apolipoprotein A-I (ApoA-I) is the best lipoprotein discriminator of CHD risk in non-diabetic populations, but the issue has never been investigated in type 2 diabetes.

Methods

In 2,627 participants without known vascular disease in the Collaborative Atorvastatin Diabetes Study, ApoB, ApoA-I, LDL-cholesterol (LDLC) and HDL-cholesterol (HDLC) were assayed at baseline.

Results

There were 108 CHD and 59 stroke endpoints over 3.9 years. The ApoB:A-I ratio at baseline was the lipoprotein variable most closely predicting CHD risk both by comparison of the hazard ratio for a 1 SD change or tertiles of frequency distribution. The areas under the receiver–operator curve for the ApoB:ApoA-I and the LDLC to HDL-HDLC ratios, although not significantly different from each other, were greater (p = 0.0005 and p = 0.0125 respectively) than that of non-HDLC:HDLC. The 27% decrease in the ApoB:ApoA-I ratio on atorvastatin predicted a 32% (95% CI 5.4–51.2%) risk reduction in CHD, close to the 36% decrease observed. Neither the ApoB:ApoA-I nor any other lipoprotein concentration or ratio predicted the stroke outcome.

Conclusions/interpretation

Overall, the ApoB:ApoA-I ratio improved on the non-HDLC:HDLC ratio in predicting CHD, but, depending on the assessment chosen, its superiority over LDLC:HDLC may be marginal. The statin-induced decrease in stroke risk may not be lipoprotein mediated.
Trial registration: ClinicalTrials.gov NCT00327418
Funding: The study was supported by unrestricted grants from Diabetes UK, the Department of Health and Pfizer to the University of Manchester and to University College, London.
Literatur
1.
Zurück zum Zitat Havel RJ, Goldstein JL, Brown MS (1980) Lipoproteins and lipid transport. In: Bondy PK, Rosenberg LE (eds) Metabolic control and disease. Saunders, Philadelphia, pp 393–494 Havel RJ, Goldstein JL, Brown MS (1980) Lipoproteins and lipid transport. In: Bondy PK, Rosenberg LE (eds) Metabolic control and disease. Saunders, Philadelphia, pp 393–494
2.
Zurück zum Zitat Fredrickson DS (1974) Plasma lipoproteins and apolipoproteins. In: The Harvey Lectures 1972–73, Series 68. Academic, London, pp 185–237 Fredrickson DS (1974) Plasma lipoproteins and apolipoproteins. In: The Harvey Lectures 1972–73, Series 68. Academic, London, pp 185–237
3.
Zurück zum Zitat Barter PJ, Ballantyne CM, Carmena R et al (2006) Apo B versus cholesterol to estimate cardiovascular risk and to guide therapy: report of the Thirty Person/Ten Country Panel. J Int Med 259:247–258CrossRef Barter PJ, Ballantyne CM, Carmena R et al (2006) Apo B versus cholesterol to estimate cardiovascular risk and to guide therapy: report of the Thirty Person/Ten Country Panel. J Int Med 259:247–258CrossRef
4.
Zurück zum Zitat Austin MA, Breslow JL, Hennekens CH, Buring JE, Willett WC, Krauss RM (1988) Low density lipoprotein subclass patterns and risk of myocardial infarction. J Am Med Assoc 260:1917–1921CrossRef Austin MA, Breslow JL, Hennekens CH, Buring JE, Willett WC, Krauss RM (1988) Low density lipoprotein subclass patterns and risk of myocardial infarction. J Am Med Assoc 260:1917–1921CrossRef
5.
Zurück zum Zitat Neary R, Bhatnagar D, Durrington PN, Ishola M, Mackness M, Arrol S (1991) An investigation of the role of lecithin: cholesterol acyl transferase and triglyceride-rich lipoproteins in the metabolism of pre-beta high density lipoproteins. Atherosclerosis 89:35–48PubMedCrossRef Neary R, Bhatnagar D, Durrington PN, Ishola M, Mackness M, Arrol S (1991) An investigation of the role of lecithin: cholesterol acyl transferase and triglyceride-rich lipoproteins in the metabolism of pre-beta high density lipoproteins. Atherosclerosis 89:35–48PubMedCrossRef
6.
Zurück zum Zitat Warnick GR, Nauck M, Rifai N (2001) Evolution of methods for measurement of HDL-cholesterol: from ultracentrifugation to homogeneous assays. Clin Chem 47:1579–1596PubMed Warnick GR, Nauck M, Rifai N (2001) Evolution of methods for measurement of HDL-cholesterol: from ultracentrifugation to homogeneous assays. Clin Chem 47:1579–1596PubMed
7.
Zurück zum Zitat Durrington PN, Bolton CH, Hartog M (1978) Serum and lipoprotein apolipoprotein B levels in normal subjects and patients with hyperlipoproteinaemia. Clin Chim Acta 82:151–160PubMedCrossRef Durrington PN, Bolton CH, Hartog M (1978) Serum and lipoprotein apolipoprotein B levels in normal subjects and patients with hyperlipoproteinaemia. Clin Chim Acta 82:151–160PubMedCrossRef
8.
Zurück zum Zitat Sniderman A, Shapiro S, Marpole D, Skinner B, Teng B, Kwiterovich POJ (1980) Association of coronary atherosclerosis with hyperapobetalipoproteinemia (increased protein but normal cholesterol levels in human plasma low density (beta) lipoproteins). Proc Natl Acad Sci U S A 77:604–608PubMedCrossRef Sniderman A, Shapiro S, Marpole D, Skinner B, Teng B, Kwiterovich POJ (1980) Association of coronary atherosclerosis with hyperapobetalipoproteinemia (increased protein but normal cholesterol levels in human plasma low density (beta) lipoproteins). Proc Natl Acad Sci U S A 77:604–608PubMedCrossRef
9.
Zurück zum Zitat Griffin BA, Minihane AM, Furlonger N et al (1999) Inter-relationships between small, dense low-density lipoprotein (LDL), plasma triacylglycerol and LDL apoprotein B in an atherogenic lipoprotein phenotype in free-living subjects. Clin Sci 97:267–276CrossRef Griffin BA, Minihane AM, Furlonger N et al (1999) Inter-relationships between small, dense low-density lipoprotein (LDL), plasma triacylglycerol and LDL apoprotein B in an atherogenic lipoprotein phenotype in free-living subjects. Clin Sci 97:267–276CrossRef
10.
Zurück zum Zitat Avogaro P, Bittolo-Bon G, Avogaro G, Cazzolato G, Quinci GB (1979) Are apolipoproteins better discriminators than lipids for atherosclerosis. Lancet 1:901–903PubMedCrossRef Avogaro P, Bittolo-Bon G, Avogaro G, Cazzolato G, Quinci GB (1979) Are apolipoproteins better discriminators than lipids for atherosclerosis. Lancet 1:901–903PubMedCrossRef
11.
Zurück zum Zitat Yusuf S, Hawken S, Öunpuu S et al (2004) INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case–control study. Lancet 364:937–952PubMedCrossRef Yusuf S, Hawken S, Öunpuu S et al (2004) INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case–control study. Lancet 364:937–952PubMedCrossRef
12.
Zurück zum Zitat Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E (2001) High apolipoprotein B, low apolipoprotein A-1, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet 358:2026–2033PubMedCrossRef Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E (2001) High apolipoprotein B, low apolipoprotein A-1, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet 358:2026–2033PubMedCrossRef
13.
Zurück zum Zitat Thompson A, Danesh J (2006) 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 259:481–492PubMedCrossRef Thompson A, Danesh J (2006) 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 259:481–492PubMedCrossRef
14.
Zurück zum Zitat Ingelsson E, Schaefer EJ, Contois JH et al (2007) Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. JAMA 298:776–785PubMedCrossRef Ingelsson E, Schaefer EJ, Contois JH et al (2007) Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. JAMA 298:776–785PubMedCrossRef
15.
Zurück zum Zitat Kastelein JJP, Van der Steeg WA, Holme I et al (2008) Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment. Circulation 117:3002–3009PubMedCrossRef Kastelein JJP, Van der Steeg WA, Holme I et al (2008) Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment. Circulation 117:3002–3009PubMedCrossRef
16.
Zurück zum Zitat Colhoun HM, Thomason MJ, Mackness MI et al (2002) Collaborative AtoRvastatin Diabetes Study (CARDS). Design of the Collaborative AtoRvastatin Diabetes Study (CARDS) in patients with type 2 diabetes. Diabet Med 19:201–211PubMedCrossRef Colhoun HM, Thomason MJ, Mackness MI et al (2002) Collaborative AtoRvastatin Diabetes Study (CARDS). Design of the Collaborative AtoRvastatin Diabetes Study (CARDS) in patients with type 2 diabetes. Diabet Med 19:201–211PubMedCrossRef
17.
Zurück zum Zitat Colhoun HM, Betteridge DJ, Durrington PN et al (2004) Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): a multicentre randomized placebo-controlled trial. Lancet 364:685–696PubMedCrossRef Colhoun HM, Betteridge DJ, Durrington PN et al (2004) Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): a multicentre randomized placebo-controlled trial. Lancet 364:685–696PubMedCrossRef
18.
Zurück zum Zitat Colhoun H, Betteridge DJ, Durrington PN et al (2005) Rapid emergence of effect of atorvastatin on cardiovascular outcomes in the Collaborative Atorvastatin Diabetes Study (CARDS). Diabetologia 48:2482–2485PubMedCrossRef Colhoun H, Betteridge DJ, Durrington PN et al (2005) Rapid emergence of effect of atorvastatin on cardiovascular outcomes in the Collaborative Atorvastatin Diabetes Study (CARDS). Diabetologia 48:2482–2485PubMedCrossRef
19.
Zurück zum Zitat Albers JJ, Marcovina SM, Kennedy H (1992) International Federation of Clinical Chemistry standardization project for measurements of apolipoproteins A-I and B. II. Evaluation and selection of candidate reference materials. Clin Chem 38:658–662PubMed Albers JJ, Marcovina SM, Kennedy H (1992) International Federation of Clinical Chemistry standardization project for measurements of apolipoproteins A-I and B. II. Evaluation and selection of candidate reference materials. Clin Chem 38:658–662PubMed
20.
Zurück zum Zitat Warnick GR, Albers JJ (1978) A comprehensive evaluation of the heparin–manganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res 19:65–76PubMed Warnick GR, Albers JJ (1978) A comprehensive evaluation of the heparin–manganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res 19:65–76PubMed
21.
Zurück zum Zitat Friedewald WT, Levy RI, Frederickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502PubMed Friedewald WT, Levy RI, Frederickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502PubMed
22.
Zurück zum Zitat De Long ER, De Long DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic corves: a nonparametric approach. Biometrics 44:837–845CrossRef De Long ER, De Long DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic corves: a nonparametric approach. Biometrics 44:837–845CrossRef
23.
Zurück zum Zitat Grundy SM, Cleeman JI, Bairey Merz CN et al (2004) For the Co-ordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation 110:227–239PubMedCrossRef Grundy SM, Cleeman JI, Bairey Merz CN et al (2004) For the Co-ordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation 110:227–239PubMedCrossRef
24.
Zurück zum Zitat Graham I, Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts) (2007) European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Atherosclerosis 194:1–45PubMedCrossRef Graham I, Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts) (2007) European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Atherosclerosis 194:1–45PubMedCrossRef
25.
Zurück zum Zitat McElduff P, Jaefarnezhad M, Durrington P (2006) American, British and European recommendations for statins in the primary prevention of cardiovascular disease applied to British men studied prospectively. Heart 92:1213–1218PubMedCrossRef McElduff P, Jaefarnezhad M, Durrington P (2006) American, British and European recommendations for statins in the primary prevention of cardiovascular disease applied to British men studied prospectively. Heart 92:1213–1218PubMedCrossRef
26.
Zurück zum Zitat Gotto A Jr, Whitney E, Stein EA et al (2000) Relation between baseline and on-treatment lipid parameters and first acute coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation 101:477–484PubMed Gotto A Jr, Whitney E, Stein EA et al (2000) Relation between baseline and on-treatment lipid parameters and first acute coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation 101:477–484PubMed
27.
Zurück zum Zitat Pepe MS, Janes H, Longton G, Leisenring W, Newcomb P (2004) Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker. Am J Epidemiol 159:882–890PubMedCrossRef Pepe MS, Janes H, Longton G, Leisenring W, Newcomb P (2004) Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker. Am J Epidemiol 159:882–890PubMedCrossRef
28.
Zurück zum Zitat Cholesterol Treatment Trialists’ (CTT) Collaborators (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366:1267–1278CrossRef Cholesterol Treatment Trialists’ (CTT) Collaborators (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366:1267–1278CrossRef
29.
Zurück zum Zitat Amarenco P, Labreuche J, Lavallee P, Touboul PJ (2004) Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke 35:2902–2909PubMedCrossRef Amarenco P, Labreuche J, Lavallee P, Touboul PJ (2004) Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke 35:2902–2909PubMedCrossRef
30.
Zurück zum Zitat The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators (2006) High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 355:549–559CrossRef The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators (2006) High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 355:549–559CrossRef
31.
Zurück zum Zitat Kurth T, Everett BM, Buring JE, Kase CS, Ridker PM, Gaziano JM (2007) Lipid levels and the risk of ischemic stroke in women. Neurology 68:556–562PubMedCrossRef Kurth T, Everett BM, Buring JE, Kase CS, Ridker PM, Gaziano JM (2007) Lipid levels and the risk of ischemic stroke in women. Neurology 68:556–562PubMedCrossRef
32.
Zurück zum Zitat Lewington S, Whitlock G, Clarke R et al (2007) Prospective Studies Collaboration: blood cholesterol and vascular mortality by age, sex and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 370:1829–1839PubMedCrossRef Lewington S, Whitlock G, Clarke R et al (2007) Prospective Studies Collaboration: blood cholesterol and vascular mortality by age, sex and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 370:1829–1839PubMedCrossRef
33.
Zurück zum Zitat Schaefer EJ, McNamara JR, Asztalos BF et al (2005) Effects of atorvastatin versus other statins on fasting and postprandial C-reactive protein and lipoprotein-associated phospholipase A2 in patients with coronary heart disease versus control subjects. Am J Cardiol 95:1025–1032PubMedCrossRef Schaefer EJ, McNamara JR, Asztalos BF et al (2005) Effects of atorvastatin versus other statins on fasting and postprandial C-reactive protein and lipoprotein-associated phospholipase A2 in patients with coronary heart disease versus control subjects. Am J Cardiol 95:1025–1032PubMedCrossRef
Metadaten
Titel
Apolipoproteins, cardiovascular risk and statin response in type 2 diabetes: the Collaborative Atorvastatin Diabetes Study (CARDS)
verfasst von
V. Charlton-Menys
D. J. Betteridge
H. Colhoun
J. Fuller
M. France
G. A. Hitman
S. J. Livingstone
H. A. W. Neil
C. B. Newman
M. Szarek
D. A. DeMicco
P. N. Durrington
Publikationsdatum
01.02.2009
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 2/2009
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-008-1176-8

Weitere Artikel der Ausgabe 2/2009

Diabetologia 2/2009 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.