Simvastatin Lowers C-Reactive Protein Within 14 Days An Effect Independent of Low-Density Lipoprotein Cholesterol Reduction

• Published in: Circulation (New York, N.Y.) Vol. 106; no. 12; pp. 1447 - 1452
• Main Authors: Plenge, Julie K., Hernandez, Teri L., Weil, Kathleen M., Poirier, Paul, Grunwald, Gary K., Marcovina, Santica M., Eckel, Robert H.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 17.09.2002; American Heart Association, Inc
• Subjects: Adult; Aged; Biological and medical sciences; C-Reactive Protein - analysis; Cholesterol, LDL - blood; Cross-Over Studies; Double-Blind Method; Female; Fibrinogen - analysis; General and cellular metabolism. Vitamins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hyperlipoproteinemias - blood; Hyperlipoproteinemias - diagnosis; Hyperlipoproteinemias - drug therapy; Kinetics; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Simvastatin - pharmacology; Simvastatin - therapeutic use; Human; Prognosis; Enzyme; Hydroxymethylglutaryl-CoA synthase; Simvastatin; Enzyme inhibitor; Metabolic diseases; Cholesterol LDL; Lipids; Hyperlipoproteinemia; Lyases; Inflammation; Statin derivative; Oxo-acid-lyases; Carbon-carbon lyases; Chemotherapy; Hypercholesterolemia; Treatment; Follow up study; Dyslipemia; C reactive protein; Antilipemic agent
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/01.CIR.0000029743.68247.31

Background— The early response of C-reactive protein to initiation of a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) is not known. The purpose of this study was to determine the rate at which highly sensitive C-reactive protein (hsCRP) levels change after initiation of simvastatin and whether this occurs independently of the change in LDL cholesterol. Methods and Results— The study was a crossover, double-blind design including 40 subjects with elevated LDL cholesterol. Subjects were randomly assigned to 1 of 2 groups: simvastatin 40 mg for 14 days, then placebo for 14 days, or placebo first, then simvastatin. Simvastatin decreased LDL cholesterol by 56±4 mg/dL ( P <0.0001) at day 7 and by an additional 8±3 mg/dL ( P =0.02) at day 14. Baseline log(hsCRP) levels were similar in the 2 groups. By day 14, log(hsCRP) was significantly lower in patients on simvastatin when compared with placebo ( P =0.011). Although there was no significant difference in fibrinogen levels, simvastatin produced a modest increase in log[lipoprotein(a)] ( P =0.03) at days 7 and 14. There were no relationships between the decrease in LDL cholesterol and the decrease in hsCRP. Conclusions— Simvastatin lowers hsCRP by 14 days, independent of its effect on LDL cholesterol. This rapid impact of a statin on hsCRP has potential implications in the management of acute coronary syndromes.