Received on June 18, 2008
Accepted on October 24, 2008

Lipids, Lipoproteins, and Cardiovascular Risk Factors

Targets of Statin Therapy: LDL Cholesterol, Non-HDL Cholesterol, and Apolipoprotein B in Type 2 Diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS)

¹ University of Manchester Cardiovascular Research Group, Manchester, UK
² Department of Medicine, Jules Thorne Institute, The Middlesex Hospital, London, UK
³ Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, Scotland, UK
⁴ Department of Epidemiology and Public Health, University College London, London, UK
⁵ Department of Clinical Biochemistry, Manchester Royal Infirmary, Manchester, UK
⁶ Centre for Diabetes and Metabolic Medicine, Barts and the London School of Medicine, University of London, London, UK
⁷ Division of Public Health and Primary Health Care, Oxford University, Oxford, UK
⁸ Department of Medicine, New York University, School of Medicine, New York, NY
⁹ Pfizer Global Pharmaceuticals, New York, NY

^* To whom correspondence should be addressed. E-mail: pdurrington{at}manchester.ac.uk.

BACKGROUND: LDL can vary considerably in its cholesterol content; thus, lowering LDL cholesterol (LDLC) as a goal of statin treatment implies the existence of considerable variation in the extent to which statin treatment removes circulating LDL particles. This consideration is particularly applicable in diabetes mellitus, in which LDL is frequently depleted of cholesterol.

METHODS: Type 2 diabetes patients randomly allocated to 10 mg/day atorvastatin (n = 1154) or to placebo (n = 1196) for 1 year were studied to compare spontaneous and statin-induced apolipoprotein B (apo B) concentrations (a measure of LDL particle concentration) at LDLC and non-HDL cholesterol (non-HDLC) concentrations proposed as statin targets in type 2 diabetes.

RESULTS: Patients treated with atorvastatin produced lower serum apo B concentrations at any given LDLC concentration than patients on placebo. An LDLC concentration of 1.8 mmol/L (70 mg/dL) during atorvastatin treatment was equivalent to a non-HDLC concentration of 2.59 mmol/L (100 mg/dL) or an apo B concentration 0.8 g/L. At the more conservative LDLC targets of 2.59 mmol/L (100 mg/dL) and 3.37 mmol/L (130 mg/dL) for non-HDLC, however, the apo B concentration exceeded the 0.9-g/L value anticipated in the recent Consensus Statement from the American Diabetes Association and the American College of Cardiology.

CONCLUSIONS: The apo B concentration provides a more consistent goal for statin treatment than the LDLC or non-HDLC concentration.