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

Diabetologia. 2009 Feb;52(2):218-25. doi: 10.1007/s00125-008-1176-8. Epub 2008 Oct 30.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apolipoprotein A-I / blood
  • Apolipoproteins / blood*
  • Atorvastatin
  • Biomarkers / blood
  • Blood Pressure / drug effects
  • Cardiovascular Diseases / epidemiology*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Angiopathies / epidemiology*
  • Double-Blind Method
  • Female
  • Heart Rate
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Pyrroles / therapeutic use*
  • Risk Factors
  • Triglycerides / blood

Substances

  • Apolipoprotein A-I
  • Apolipoproteins
  • Biomarkers
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Triglycerides
  • Atorvastatin

Associated data

  • ClinicalTrials.gov/NCT00327418