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Apolipoproteins, cardiovascular risk and statin response in type 2 diabetes: the Collaborative Atorvastatin Diabetes Study (CARDS).
Charlton-Menys, V, Betteridge, D, Colhoun, H, Fuller, J, France, MM, Hitman, G, Livingstone, S, Neil, H, Newman, C, Szarek, M, DeMicco, D, Durrington, PN
Diabetologia. 2009;52( 2).
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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 HDLC [corrected] 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.
Keyword(s)
Adult; Aged; Double-Blind Method; Female; Heart Rate; Humans; Male; Middle Aged; Risk Factors; blood: Apolipoprotein A-I; blood: Apolipoproteins; blood: Biological Markers; blood: Diabetes Mellitus, Type 2; blood: Triglycerides; drug effects: Blood Pressure; epidemiology: Cardiovascular Diseases; epidemiology: Diabetic Angiopathies; epidemiology: Myocardial Infarction; therapeutic use: Heptanoic Acids; therapeutic use: Hydroxymethylglutaryl-CoA Reductase Inhibitors; therapeutic use: Pyrroles