Statin Therapy, LDL Cholesterol, C-Reactive Protein, and Coronary Artery Disease
Steven E. Nissen, M.D., E. Murat Tuzcu, M.D., Paul Schoenhagen, M.D., Tim Crowe, B.S., William J. Sasiela, Ph.D., John Tsai, M.D., John Orazem, Ph.D., Raymond D. Magorien, M.D., Charles O'Shaughnessy, M.D., Peter Ganz, M.D., for the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) Investigators
Background Recent trials have demonstrated better outcomes withintensive than with moderate statin treatment. Intensive treatmentproduced greater reductions in both low-density lipoprotein(LDL) cholesterol and C-reactive protein (CRP), suggesting arelationship between these two biomarkers and disease progression.
Methods We performed intravascular ultrasonography in 502 patientswith angiographically documented coronary disease. Patientswere randomly assigned to receive moderate treatment (40 mgof pravastatin orally per day) or intensive treatment (80 mgof atorvastatin orally per day). Ultrasonography was repeatedafter 18 months to measure the progression of atherosclerosis.Lipoprotein and CRP levels were measured at baseline and follow-up.
Results In the group as a whole, the mean LDL cholesterol levelwas reduced from 150.2 mg per deciliter (3.88 mmol per liter)at baseline to 94.5 mg per deciliter (2.44 mmol per liter) at18 months (P<0.001), and the geometric mean CRP level decreasedfrom 2.9 to 2.3 mg per liter (P<0.001). The correlation betweenthe reduction in LDL cholesterol levels and that in CRP levelswas weak but significant in the group as a whole (r=0.13, P=0.005),but not in either treatment group alone. In univariate analyses,the percent change in the levels of LDL cholesterol, CRP, apolipoproteinB-100, and nonhigh-density lipoprotein cholesterol wererelated to the rate of progression of atherosclerosis. Afteradjustment for the reduction in these lipid levels, the decreasein CRP levels was independently and significantly correlatedwith the rate of progression. Patients with reductions in bothLDL cholesterol and CRP that were greater than the median hadsignificantly slower rates of progression than patients withreductions in both biomarkers that were less than the median(P=0.001).
Conclusions For patients with coronary artery disease, the reducedrate of progression of atherosclerosis associated with intensivestatin treatment, as compared with moderate statin treatment,is significantly related to greater reductions in the levelsof both atherogenic lipoproteins and CRP.
Source Information
From the Cleveland Clinic Foundation, Cleveland (S.E.N., E.M.T., P.S., T.C.); Pfizer, New York (W.J.S., J.T., J.O.); Ohio State University Medical Center, Columbus (R.D.M.); North Ohio Heart Care, Elyria (C.O.); and Brigham and Women's Hospital, Boston (P.G.).
Address reprint requests to Dr. Nissen at the Department of Cardiovascular Medicine, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, or at nissens{at}ccf.org.
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