Rosuvastatin Reduces Plasma Small Dense Ldl-Cholesterol Predominantly in Non-Diabetic Hypercholesterolemic Patients


Aims: Small dense LDL (sdLDL) cholesterol is considered a cardiovascular risk. Our purpose in this study was to evaluate the efficacy of rosuvastatin in reducing sdLDL and large buoyant LDL (lbLDL-C) in hypercholesterolemia. Methods: Fifty-six patients with a mean baseline LDL-cholesterol (LDL-C) concentration of 173.9 ± 40.5 mg/dL were treated with rosuvastatin 2.5 mg/day for 12 weeks. LDL-C, sdLDL-C, and apolipoprotein (apo) B were assessed and l lbLDL-C was calculated (LDL-C minus sdLDL-C). Results: After 12-week treatment with rosuvastatin 2.5mg, sdLDL-C and lbLDL-C were significantly reduced from 62.1 ± 23.8 mg/dL to 34.0 ± 13.4 mg/dL, p <0.001 and 112.7 ± 34.9 mg/dL to 77.2± 29.2 mg/dL, p < 0.001 respectively, and sdLDL-C/lbLDL-C ratio and apo B also decreased significantly, from 0.36 ± 0.02 to 0.32 ± 0.02, p < 0.005 and 134.2 ± 4.3 to 93.6 ± 3.5 mg/dl, p < 0.001, respectively. In diabetic subjects there was significant correlation between percent reductions in the plasma triglyceride and sdLDL-C/ lbLDL-C ratio (r = 0.58, p < 0.005), but not between the percentage decrease in plasma triglyceride and sdLDL-C. Conclusions: Treatment with rosuvastatin is associated with significant reduction in sdLDL, lbLDL and sdLDL/lbLDL ratio.

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G. Yoshino, S. Nakano, T. Matsumoto, E. Murakami, T. Morita and K. Kuboki, "Rosuvastatin Reduces Plasma Small Dense Ldl-Cholesterol Predominantly in Non-Diabetic Hypercholesterolemic Patients," Pharmacology & Pharmacy, Vol. 3 No. 1, 2012, pp. 72-78. doi: 10.4236/pp.2012.31011.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] S. M. Grundy, J. I. Cleeman, C. N. Merz, H. B. Brewer Jr., L. T. Clark, D. B. Hunninghake, R. C. Pasternak, S. C. Smith Jr. and N. J. Stone, “Coordinating Committee of the National Cholesterol Education Program, Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines,” Journal of the American College of Cardiology, Vol. 44, No. 3, 2004, pp. 720-32. doi:10.1016/j.jacc.2004.07.001
[2] Lipid Research Clinics Program, “The Lipid Research Clinics Primary Prevention Trial Results. II, The Relationship of Reduc-tion in Incidence of Coronary Heart Disease to Cholesterol Lowering,” Journal of the American Medical Association (JAMA), Vol. 251, No. 3, 1984, pp. 365-374. doi:10.1001/jama.1984.03340270043026
[3] M. A. Austin, J. L. Breslow, C. H. Hennekens, J. E. Buring, W. C. Willett and R. M. Krauss, “Low-Density Lipoprotein Subclass Patterns and Risk of Myocardial Infarction,” Journal of the American Medical Association (JAMA), Vol. 260, No. 13, 1988, pp. 1917-1921. doi:10.1001/jama.1988.03410130125037
[4] B. A. Griffin, D. J. Freeman, G. W. Tait, J. Thomson, M. J. Caslake, C. J. Packard and J. Shepherd, “Role of Plasma Triglyceride in the Regulation of Plasma Low Density Lipoprotein (LDL) Subfractions: Relative Contribution of Small Dense LDL to Coronary Heart Disease Risk,” Atherosclerosis, Vol. 106, No. 2, 1994, pp. 241- 253. doi:10.1016/0021-9150(94)90129-5
[5] T. Hirano, Y. Ito Y, S. Koba, M. Toyoda, A. Ikejiri, H. Saegusa, J. Ya-mazaki and G. Yoshino, “Clinical Significance of Small Dense Low-Density Lipoprotein Cholesterol Levels Determined by the Simple Precipitation Method,” Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 24, No. 3, 2004, pp. 558-563. doi:10.1161/01.ATV.0000117179.92263.08
[6] T. No-zue, I. Michishita, Y. Ito and T. Hirano, “Effects of Statin on Small Dense Low Density-Lipoprotein Cholesterol and Remnant-Like Particle Cholesterol in Heterozygous Hypercholesterolemia,” Journal of Atherosclerosis and Thrombosis, Vol.15, No. 3, 2008, pp. 146- 153. doi:10.5551/jat.E552
[7] A. Tokuno, T. Hirano, T. Hayashi, Y. Mori, T. Yamamoto, M. Nagashima, Y. Shiraishi, Y. Ito and M. Adachi, “The Effects of Statin and Fibrate on Lowering Small Dense LDL-Cholesterol in Hy-perlipidemic Patients with Type 2 Diabetes,” Journal of Atherosclerosis and Thrombosis, Vol. 14, No. 3, 2007, pp. 128-132. doi:10.5551/jat.14.128
[8] A. Ikejiri, T. Hirano, S. Mu-rayama, G. Yoshino, N. Gushiken, T. Hyodo, T. Taira and M. Adachi, “Effects of Atorvastatin on Triglyceride-Rich Lipoproteins, Low- Density Lipoprotein Sub-class, and C-Reactive Protein in Hemodialysis Patients,” Metabolism, Vol. 53, No. 9, 2004, pp. 1113-1117. doi:10.1016/j.metabol.2004.01.011
[9] R. C. Turner, R. R. Holman, H. Millns, H. A. Neil, I. M. Stratton, S. E. Manley and D. R. Matthews, “Risk Factors for Coronary Artery Disease in Non-Insulin Dependent Diabetes Mellitus: UK Prospective Diabetes Study (UKPDS 23),” British Medical Journal (BMJ), Vol. 316, No. 7134, 1998, pp. 823-828. doi:10.1136/bmj.316.7134.823
[10] K. R. Feingold, C. Grunfeld, M. Pan, W. Doerrler and R. M. Krauss, “LDL Subclass Phenotypes and Triglyceride Metabolism in Non-Insulin-Dependent Diabetes,” Arteriosclerosis, Thrombosis, Vol. 12, No. 12, 1992, pp. 1496-1502. doi:10.1161/01.ATV.12.12.1496
[11] T. Hirano, K. Oi, S. Sakai, K. Kashiwazaki, M. Adachi and G. Yoshino, “High Prevalence of Small LDL in Diabetic Nephropathy Is Not Directly Associated with Kidney Damage: A Possible Role of Postprandial Lipemia,” Atherosclerosis, Vol. 141, No. 1, 1998, pp. 77-85. doi:10.1016/S0021-9150(98)00150-6
[12] T. Hirano, Y. Ito, H. Saegusa and G. Yoshino, “A Novel and Simple Method for Quantification of Small Dense Low-Density Lipoprotein,” Journal of Lipid Research, Vol. 44, No.11. 2003, pp. 2193-2201. doi:10.1194/jlr.D300007-JLR200
[13] M. Okada, H. Matsui, Y. Ito, A. Fujiwara and K. Inano, “Low-Density Lipoprotein Can Be Chemically Measured: A New Superior Method,” Journal of Laboratory and Clinical Medicine, Vol. 132, No. 3, 1998, pp. 195-201. doi:10.1016/S0022-2143(98)90168-8
[14] R. M. Krauss and D. J. Burke, “Identification of Multiple Subclass of Plasma Low Density Lipoproteins in Normal Humans,” Journal of Lipid Research, Vol. 23, 1982, pp. 97-104.
[15] I. Rajiman, M. JKenall, R. Cramb, R. L. Holder, M. Salih and M. D. Gambage, “Investigation of Low Density Lipoprotein Subfractions as a Coronary Risk Factor in Normotriglyceridemic Men,” Atherosclerosis, Vol. 125, No. 2, 1996, pp. 231-242. doi:10.1016/0021-9150(96)05881-9
[16] M. Iwai, G. Yoshino, M. Matsushita, M. Morita, K. Matsuba, T. Kazumi and S. Baba, “Abnormal Lipoprotein Composition in Normolipidemic Diabetic Patients,” Diabetes Care, Vol. 13, No. 7, 1990, pp. 792-796. doi:10.2337/diacare.13.7.792
[17] G. Yoshino, T. Hirano and T. Kazumi, “Atherogenic Lipoproteins and Diabetes Melltus,” Journal of Diabetes and its Complications, Vol. 16, No. 1, 2002, pp. 29-34. doi:10.1016/S1056-8727(01)00199-4
[18] S. Koba, Y. Yokota, T. Hirano, Y. Ito, Y. Ban, F. Tsunoda, T. Sato, M. Shoji, H. Suzuki, E. Genshi, Y. Kobayashi and T. Katagiri, “Small LDL-Cholesterol Is Superior to LDL-Cholesterol for Determinin Severe Coronary Atherosclerosis,” Journal of Atherosclerosis and Thrombosis, Vol. 15, No. 5, 2008, pp. 250-260. doi:10.5551/jat.E572
[19] G. Yoshino, T. Hirano and T. Kazumi, “Treatment of Small Dense LDL,” Journal of Atherosclerosis and Thrombosis, Vol. 9, No. 6, 2002, pp.:266-275. doi:10.5551/jat.9.266
[20] M. J. Caslake, G. Stwart, S. P. Day, E. Daly, F. McTaggart, M. J. Chapman, P. Durrington, P. Laggner, M. Mackness, J. Pears and C. J. Packard, “Phenotype-Dependent and -Independendent Actions of Rosuvastatin on Atherogenc Lipoprotein Subfractions in Hyperlipidaemia,” Atherosclerosis, Vol. 171, No. 2, 2003, pp. 245- 253. doi:10.1016/j.atherosclerosis.2003.08.025
[21] M. S. Kostapanos, H. J. Milionis, T. D. Filippatos, E. S. Nakou, E. T. Baikaktari, A. D. Tselepis and M. S. Elisaf, “A 12-Weeks, Prospective, Open-Label Analysis of the Effect of Rosuvastatin on Triglyceride-Rich Lipoprotein Metabolism in Patients with Primary Dyslipidemia,” Clinical Therapeutics, Vol. 29, No. 7, 2007, pp. 1403- 1414. doi:10.1016/j.clinthera.2007.07.019
[22] M. S. Kostapanos, H. J. Milionis, K. G. Lagos, C. B. Rizos, A. D. Tselepis and M. S. Elisaf, “Baseline Triglyceride Levels and Insulin Sensitivity Are Major Determinants of the Increase of LDL Particle Size and Buoyancy Induced by Rosuvastatin Treatment in Patients with Primary Hyper-lipidemia,” European Journal of Pharmacology, Vol. 590, No. 1-3, 2008, pp.327-332. doi:10.1016/j.ejphar.2008.06.007
[23] A. G. Olsson, H. Istad, O. Luurila, S. Stender, J. Tuomilehto, O. Wiklund, H. Southworth, J. Pears and J. W. Wilpshaar, on Behalf of the Rosuvastatin Investigators Group, “Effect of Rosuvastatin and Atorvastatin Compared over 52 Weeks of Treatment in Patients with Hypercholesterolemia,” American Heart Journal, Vol. 144, No. 6, 2002, pp. 1044-1051. doi:10.1067/mhj.2002.128049
[24] T. J. Knott, R. J. Pease, L. M. Powell, S. C. Wallis, S. C. Rall Jr., T. L. Inerarity, B. Blackhart, R. Marcel, D. Johnson, M. Filler, A. J. Lusis, B. J. MCarthy, R. W. Mahley, B. Levy-Wilson and J. Scott, “Complete Protein Sequence and Identification of Structural Domains of Human Apolipoprotein B,” Nature, Vol. 323, No. 6090, 1986, pp. 734-738. doi:10.1038/323734a0
[25] B. A. Griffin and C. J. Packard, “Metabolism of VLDL and LDL Subclasses,” Current Opinion in Lipidology, Vol. 5, No. 3, 1994, pp. 200-206. doi:10.1097/00041433-199405030-00007
[26] B. A. Griffin, “Low-Density Lipoprotein Subclasses: Mechanisms of Formation and Modulation,” Proceedings of the Nutrition Society, Vol. 56, No. 2, 1997, pp. 693-702. doi:10.1079/PNS19970069

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