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

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.