Arzneimittelforschung 2009; 59(9): 445-450
DOI: 10.1055/s-0031-1296423
Lipid Regulating Agents
Editio Cantor Verlag Aulendorf (Germany)

Effects of Increasing the Dose of Pravastatin on Serum Adiponectin Level in Japanese Mild Hypercholesterolemic and Hypertensive Patients

Tatsuya Kai
Department of Vascular and Geriatric Medicine, Kenilworth, Kinki University School of Medicine, Osaka, (Japan)
,
Ken Kanamasa
Department of Vascular and Geriatric Medicine, Kenilworth, Kinki University School of Medicine, Osaka, (Japan)
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Publikationsverlauf

Publikationsdatum:
13. Dezember 2011 (online)

Abstract

The plasma level of adiponectin (CAS 1070484-33-1), known as an anti-athero-genic adipocytokine, inversely correlates with the progression of atherosclerosis. The reported effects of statins on the serum level of adiponectin include significant increases in the adiponectin levels caused by pravastatin (CAS 81131-70-6). In this study, increasing the dosage of pravastatin was investigated to determine whether it had a clearly favorable effect on the adiponectin level in hypercholesterolemic patients.

A total of 26 mild hypercholesterolemic and hypertensive patients were enrolled in this study. The patients were initially treated with pravastatin 10mg/day for 6 months or more, and then increased to pravastatin 20 mg/day. Serum adiponectin, cholesterol fractionated components, and lipoprotein components were evaluated after 6 months.

Increasing the dose of pravastatin from 10 to 20 mg/day caused the low-density lipoprotein cholesterol levels to decrease (from 130 to 104 mg/dL, p < 0.001), and thereafter the serum adiponectin levels, particularly the high-molecular-weight adiponectin levels significantly increased (from 10.9 to 12.6 µg/mL, p = 0.022; from 6.6 to 7.6 µg/mL, p = 0.022, respectively).

Pravastatin increased the serum adiponectin level after increasing the dosage from 10 to 20 mg/day. It remains possible, however, that the difference was due not only to pharmacologic effects, but also to other specific characteristics such as the subject characteristics, viz.; race, body size, high-density lipoprotein cholesterol, etc.

 
  • References

  • 1 Matsuzawa Y, Funahashi T, Kihara S, Shimomura I. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol. 2004; 24: 29-33
  • 2 Murakami H, Ura N, Furuhashi M, Higashiura K, Miura T, Shimamoto K. Role of adiponectin in insulin-resistant hypertension and atherosclerosis. Hypertens Res. 2003; 26: 705-10
  • 3 Imatoh T, Miyazaki M, Momose Y, Tanihara S, Une H. Adiponectin levels associated with the development of hypertension: a prospective study. Hypertens Res. 2008; 31: 229-33
  • 4 Sugiyama S, Fukushima H, Kugiyama K, Maruyoshi H, Kojima S, Funahashi T et al. Pravastatin improved glucose metabolism associated with increasing plasma adiponectin in patients with impaired glucose tolerance and coronary artery disease. Atherosclerosis. 2007; 194: e43-e51
  • 5 Sakamoto K, Sakamoto T, Ogawa H. for the Kumamoto Joint Research on Hypercholesterolemia (KOJIROU) Investigators. The effect of 6 months of treatment with pravastatin on serum adiponectin concentrations in Japanese patients with coronary artery disease and hypercholesterolemia: a pilot study. Clin Ther. 2006; 28: 1012-21
  • 6 Inami N, Nomura S, Shouzu A, Omoto S, Kimura Y, Takahashi N et al. Effects of pitavastatin on adiponectin in patients with hyperlipidemia. Pathophysiol Haemost Thromb. 2007; 36: 1-8
  • 7 Blanco-Colio LM, Martin-Ventura JL, Gómez-Guerrero C, Masramon X, de Teresa E, Farsang C et al. Adiponectin plasma levels are increased by atorvastatin treatment in subjects at high cardiovascular risk. Eur J Pharmacol. 2008; 586: 259-65
  • 8 Koh KK, Quon MJ, Han SH, Chung WJ, Ahn JY, Seo YH et al. Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients. Circulation. 2004; 110: 3687-92
  • 9 Kai T, Arima S, Taniyama Y, Nakabou M, Kanamasa K. Comparison of the effect of lipophlic and hydrophilic statins on serum adiponectin levels in patients with mild hypertension and dyslipidemia: Kinki Adiponectin Interventional (KAI) Study. Clin Exp Hypertens. 2008; 30: 530-40
  • 10 Ando H, Sugimoto K, Yanagihara H, Tsuruoka S, Saito T, Takamura T et al. Effects of atorvastatin and pravastatin on glucose tolerance, adipokine levels and inflammatory markers in hypercholesterolaemic patients. Clin Exp Pharmacol Physiol. 2008; 35: 1012-17
  • 11 Koh KK, Quon MJ, Han SH, Chung WJ, Ahn JY, Seo YH et al. Additive benefical effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia. J Am Coll Cardiol. 2005; 45: 1649-53
  • 12 Teramoto T, Sasaki J, Ueshima H, Egusa G, Kinoshita M, Shimamoto K et al. Goals of dyslipidemia management.-executive summary of Japan Atherosclerosis Society (JAS) guideline for diagnosis and prevention of atherosclerotic cardiovascular diseases for Japanese. J Atheroscler Thromb. 2007; 14: 209-12
  • 13 Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008; 358: 1431-43
  • 14 Nakamura H, Arakawa K, Itakura H, Kitabatake A, Goto Y, Toyota T et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet. 2006; 368: 1155-63
  • 15 Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, Macfarlane PW et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995; 333: 1301-7
  • 16 Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004; 364: 685-96
  • 17 Gotto Jr AM. Establishing the benefit of statins in low-to-moderate-risk primary prevention: the Air Force/Texas Coronary Arterosclerosis Prevention Study (AFCAPS/Tex-CAPS). Atherosclerosis. 2007; 8 (suppl:) 3-8
  • 18 Sever PS, Poulter NR, Dahlöf B, Wedel H. Anglo-Scandinavian Cardiac Outcome Trial Investigators. Different time course for prevention of coronary and stroke events by atorvastatin in the Anglo-Scandinavian Cardiac Outcome Trial-Lipid-Lowering Arm (ASCOT-LLA). Am J Cardiol. 2005; 96 (5A) 39 F-44 F
  • 19 Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999; 257: 79-83
  • 20 Aso Y, Yamamoto R, Wakabayashi S, Uchida T, Takayanagi K, Takebayashi K et al. Comparison of serum high-molecular-weight (HMW) adiponectin with total adiponectin concentrations in type 2 diabetic patients with coronary artery disease using a novel enzyme-linked immunosorbent assay to detect HMW adiponectin. Diabetes. 2006; 55: 1954-60
  • 21 Kido T, Kurata H, Matsumoto A, Tobiyama R, Musha T, Hayashi K et al. Lipoprotein analysis using agarose gel electrophoresis and differential staining of lipids. J Atheroscler Thromb. 2001; 8: 7-13
  • 22 Hidaka H, Tozuka M, Meyer B, Yamauchi K, Sugano M, Nakabyashi T et al. Characterization of triglyceride rich lipoproteins with very light density by ultracentrifugation and agarose gel electrophoresis using triglyceride- and cholesterol-staining. Ann Clin Lab Sci. 2003; 33: 167-78
  • 23 Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol. 2005; 19: 117-25
  • 24 Tomas E, Tsao TS, Saha AK, Murrey HE, Zhang Cc C, Itani SI et al. Enhanced muscle fat oxidation and glucose transport by ACR30 globular domain: Acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci USA. 2002; 99: 16309-13
  • 25 Goldfine AB, Kahn CR. Adiponectine: linking the fat cell to insulin sensitivity. Lancet. 2003; 362: 1431-2
  • 26 Fisher FF, Trujillo ME, Hanif W, Barnett AH, McTernan PG, Sherer PE et al. Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males. Diabetologia. 2005; 48: 1084-7
  • 27 Hara K, Horikoshi M, Yamauchi T, Yago H, Miyazaki O, Ebinuma H et al. Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care. 2006; 29: 1357-62
  • 28 Heidemann C, Sun Q, van Dam RM, Meigs JB, Zhang C, Tworoger SS et al. Total and high-molecular-weight adiponectin and resistin in relation to the risk for type 2 diabetes in women. Ann Intern Med. 2008; 149: 307-16
  • 29 Kubota N, Yano W, Kubota T, Yamauchi T, Itoh S, Kumagai H et al. Adiponectin stimulates AMP-Activated protein kinase in the hypothalamus and increases food intake. Cell Metab. 2007; 6: 55-68
  • 30 Freeman DJ, Norrie J, Sattar N, Neely RD, Cobbe SM, Ford I et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation. 2001; 103: 357-62
  • 31 Collins R, Armitage J, Parish S, Aleigh P, Peto R. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomized placebo-controlled trial. Lancet. 2003; 361: 2005-16
  • 32 Verdecchia P, Reboldi G, Angeli F, Borgioni C, Gattobigio R, Filippucci L et al. Adverse prognostic significance of new diabetes in treated hypertensive subjects. Hypertension. 2004; 43: 963-9
  • 33 Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J et al. Disruption of adiponectin causes insurin resistance and neointimal formation. J Biol Chem. 2002; 277: 25863-6
  • 34 Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K et al. Globular adiponectin protected ob/ob mice from diabetes and Apo E-deficient mice from atherosclerosis. J Biol Chem. 2003; 278: 2461-8
  • 35 Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K et al. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation. 2004; 109: 2046-9
  • 36 Dobiásová M, Frohlich J.. The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL)). Clin Biochem. 2001; 34: 583-8
  • 37 Iwashima Y, Horio T, Kumada M, Suzuki Y, Kihara S, Rakugi H et al. Adiponectin and renal function, and implication as a risk of cardiovascular disease. Am J Cardiol. 2006; 98: 1603-8
  • 38 Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000; 102: 2165-8
  • 39 Zwaka TP, Hombach V, Torzewski J. C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation. 2001; 103: 1194-7
  • 40 Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH et al. Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators: C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005; 352: 20-8