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(Circulation. 2008;117:3002-3009.)
© 2008 American Heart Association, Inc.

Preventive Cardiology

Lipids, Apolipoproteins, and Their Ratios in Relation to Cardiovascular Events With Statin Treatment

John J.P. Kastelein, MD, PhD; Wim A. van der Steeg, MD; Ingar Holme, PhD; Michael Gaffney, PhD; Nilo B. Cater, MD; Philip Barter, MD, PhD; Prakash Deedwania, MD, PhD; Anders G. Olsson, MD, PhD; S. Matthijs Boekholdt, MD, PhD; David A. Demicco, PharmD; Michael Szarek, MS; John C. LaRosa, MD; Terje R. Pedersen, MD, PhD; Scott M. Grundy, MD, PhD, for the TNT and IDEAL Study Groups

From the Academic Medical Center, University of Amsterdam (J.J.P.K., W.A.v.d.S., S.M.B.), Amsterdam, the Netherlands; Center for Preventive Medicine, Ullevål University Hospital (I.H., T.R.P.), Oslo, Norway; Pfizer Inc (M.G., N.B.C., D.A.D., M.S.), New York, NY; the Heart Research Institute (P.B.), Sydney, Australia; Veterans Affairs Central California Healthcare System and University of California San Francisco School of Medicine (P.D.), San Francisco, Calif; University Hospital (A.G.O.), Linköping, Sweden; State University of New York Health Science Center (J.C.L.), Brooklyn, NY; and the University of Texas Southwestern Medical Center (S.M.G.), Dallas.

Reprint requests to John J.P. Kastelein, MD, PhD, Academic Medical Center, Department of Vascular Medicine, Room F4-159.2, PO Box 22660, 1100 DD, Amsterdam, the Netherlands. E-mail j.j.kastelein{at}amc.uva.nl

Received May 12, 2007; accepted March 31, 2008.

Background— Low-density lipoprotein (LDL) cholesterol is the principal target of lipid-lowering therapy, but recent evidence has suggested more appropriate targets. We compared the relationships of on-treatment levels of LDL cholesterol, non–high-density lipoprotein (HDL) cholesterol, and apolipoprotein B, as well as ratios of total/HDL cholesterol, LDL/HDL cholesterol, and apolipoprotein B/A-I, with the occurrence of cardiovascular events in patients receiving statin therapy.

Methods and Results— A post hoc analysis was performed that combined data from 2 prospective, randomized clinical trials in which 10 001 ("Treating to New Targets") and 8888 ("Incremental Decrease in End Points through Aggressive Lipid Lowering") patients with established coronary heart disease were assigned to usual-dose or high-dose statin treatment. In models with LDL cholesterol, non-HDL cholesterol and apolipoprotein B were positively associated with cardiovascular outcome, whereas a positive relationship with LDL cholesterol was lost. In a model that contained non-HDL cholesterol and apolipoprotein B, neither was significant owing to collinearity. Total/HDL cholesterol ratio and the apolipoprotein B/A-I ratio in particular were each more closely associated with outcome than any of the individual proatherogenic lipoprotein parameters.

Conclusions— In patients receiving statin therapy, on-treatment levels of non-HDL cholesterol and apolipoprotein B were more closely associated with cardiovascular outcome than levels of LDL cholesterol. Inclusion of measurements of the antiatherogenic lipoprotein fraction further strengthened the relationships. These data support the use of non-HDL cholesterol or apolipoprotein B as novel treatment targets for statin therapy. Given the absence of interventions that have been proven to consistently reduce cardiovascular disease risk through raising plasma levels of HDL cholesterol or apolipoprotein A-I, it seems premature to consider the ratio variables as clinically useful.

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CLINICAL PERSPECTIVE

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