Abstract
Background: Rapid lowering of low‐density lipoprotein (LDL) cholesterol levels as well as C‐reactive protein (CRP) by administration of drugs may produce early benefit to the coronary endothelium in patients with coronary heart disease and reduce angina and coronary events after revascularization. Limited information has been available in evaluating a potentially effective first 2‐week therapeutic approach for the treatment of patients with hypercholesterolemia using a statin.
Hypothesis: The study was undertaken to investigate whether a rapid LDL cholesterol and CRP reduction can be achieved by 2‐week simvastatin therapy using a common lipid‐lowering protocol in patients with hypercholesterolemia.
Methods: Forty‐two patients were randomly assigned to 20 or 40 mg/day of simvastatin. Blood samples were drawn at Day 0 and at Day 14 for measuring lipid profile, CRP levels, and hepatic enzymes in all patients.
Results: The results showed that both doses of simvastatin (20 and 40 mg) induced significant reductions in total cholesterol (TC, 25 and 38%) and LDL cholesterol (31 and 46%) compared with baseline. However, the highest dose of simvastatin (40 mg) resulted in significantly greater reductions in TC and LDL cholesterol (p = 0.04, p = 0.02, respectively) compared with the group receiving 20 mg (p < 0.04, p < 0.02, respectively). a less significant reduction was observed in mean triglycerides (tg) level (16 and 25%) compared with tc and ldl cholesterol. there was no significant difference in mean high‐density lipoprotein (hdl) cholesterol levels compared with baseline in either group. in addition, both doses of simvastatin induced significant reductions in mean crp levels on day 14 (22.3 and 23.1%) in a non dose‐dependent manner (p < 0.001, respectively).
Conclusions: Our data suggest that a common daily dose of simvastatin, especially 40 mg, is an effective 2‐week therapy for patients with hypercholesterolemia, and benefit to the vascular endothelium can be derived quickly by reduction of CRP levels.
Keywords: simvastatin, lipid profile, C‐reactive protein, hypercholesterolemia
Full Text
The Full Text of this article is available as a PDF (28.0 KB).
References
- 1. Jackson G: The role of statins in acute coronary syndromes: Managing the unmet need. Int J Clin Pract 2000; 54: 445–449 [PubMed] [Google Scholar]
- 2. Szucs TD: Pharmaco‐economic aspects of lipid‐lowering therapy: Is it worth the price? Eur Heart J 1998; 19 (suppl M): M22–M28 [PubMed] [Google Scholar]
- 3. Fairhurst K, Huby G: From trial data to practical knowledge: Qualitative study of how general practitioners have accessed and used evidence about statin drugs in their management of hypercholesterolaemia. Br Med J 1998; 317: 1130–1134 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Azar RR, Waters DD, Lebanon B: PRINCE's prospects: Statin, inflammation, and coronary risk. Am Heart J 2001; 141: 881–883 [DOI] [PubMed] [Google Scholar]
- 5. Treasure CB, Klein JL, Weintraub WS, Talley JD, Stillabower ME, Kosinski AS, Zhang J, Boccuzzi SJ, Cedarholm JC, Alexander RW: Beneficial effects of cholesterol‐lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med 1995; 332: 481–487 [DOI] [PubMed] [Google Scholar]
- 6. Schrott HG, Knapp H, Davila M, Shurzinske L, Black D: Effect of atorvastatin on blood lipid levels in the first 2 weeks of treatment: A randomized, placebo‐controlled study. Am Heart J 2000; 140: 249–252 [DOI] [PubMed] [Google Scholar]
- 7. Knapp HH, Schrott H, Ma P, Knapp R, Chin B, Gaziano JM, Burke SK, Davidson MH: Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia. Am J Med 2001; 110: 352–360 [DOI] [PubMed] [Google Scholar]
- 8. Dupuis J, Tardif J, Cernacek P, Théroux P: Cholesterol reduction rapidly improves endothelial function after acute coronary syndrome. J Am Coll Cardiol 1998; 31: 891–896 [DOI] [PubMed] [Google Scholar]
- 9. Arntz HR, Wunderlich W, Schnitzer L: The decisive importance of cholesterol lowering therapy for coronary lesion and clinical course immediately after an acute coronary event: Short‐ and long‐term results of a controlled study. Circulation 1998; 98 (suppl 1): 1–45 9665051 [Google Scholar]
- 10. Limacher MC, Douglas PS, Germano G, Laskey WK, Lindsay BD, McKetty MH, Moore ME, Park JK, Prigent FM, Walsh MN: Long‐term effects of pravastatin on plasma concentration of C‐reactive protein: The cholesterol and recurrent events (CARE) investigators. Circulation 1999; 100: 230–235 [DOI] [PubMed] [Google Scholar]
- 11. Miller M, Dolinor C, Cromwell W, Oivos JD: Effectiveness of high doses of simvastatin as monotherapy in mixed hyperlipidemia. Am J Cardiol 2001; 87: 232–233 [DOI] [PubMed] [Google Scholar]
- 12. Ridker PM, Rifai N, Lowenthal SP: Rapid reduction in C‐reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation 2001; 103: 1191–1193 [DOI] [PubMed] [Google Scholar]
- 13. Chen Z, Fukutomi T, Zago AC, Ehlers R, Detmers PA, Wright SD, Rogers C, Simon DI: Simvastatin reduces neointimal thickening in low‐density lipoprotein receptor‐deficient mice after experimental angioplasty without changing plasma lipids. Circulation 2002; 106: 20–23 [DOI] [PubMed] [Google Scholar]
- 14. Li J‐J, Jiang H, Huang C‐X, Fang C‐H, Tang Q‐Z, Xia H, Liu J, Li G‐S: Elevated levels of plasma C‐reactive protein in patients with unstable angina: Its relations with coronary stenosis and lipid profile. Angiology 2002; 53: 265–272 [DOI] [PubMed] [Google Scholar]
- 15. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH: Inflammation, aspirin and risks of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336: 973–979 [DOI] [PubMed] [Google Scholar]
- 16. Schrott HG, Bittner V, Vittinghoff E, Herrington DM: Adherence to National Cholesterol Education Program Treatment goals in postmeno‐pausal women with heart disease: The Heart and Estrogestin Replacement Study (HERS). J Am Med Assoc 1997; 277: 1281–1286 [PubMed] [Google Scholar]
- 17. Reed RG, Fong SY, Pearson TA: Role of a central laboratory in implementing National Cholesterol Education Panel guidelines in rural practices: Model system for managed care. Clin Chem 1995; 41: 271–274 [PubMed] [Google Scholar]