title: The effects of pitavastatin, eicosapentaenoic acid and combined therapy on platelet-derived microparticles and adiponectin in hyperlipidemic, diabetic patients.
abstract: Platelet-derived microparticles (PDMP) play an important role in the pathogenesis of diabetic vasculopathy, and statins or eicosapentaenoic acid (EPA) have been shown to have a beneficial effect on atherosclerosis in hyperlipidemic patients. However, the influence of EPA and statins on PDMP and adiponectin in atherosclerosis is poorly understood. We investigated the effect of pitavastatin and EPA on circulating levels of PDMP and adiponectin in hyperlipidemic patients with type II diabetes. A total of 191 hyperlipidemic patients with type II diabetes were divided into three groups: group A received pitavastatin 2 mg once daily (n = 64), group B received EPA 1800 mg daily (n = 55) and group C received both drugs (n = 72). PDMP and adiponectin were measured by ELISA at baseline and after 3 and 6 months of drug treatment. Thirty normolipidemic patients were recruited as healthy controls. PDMP levels prior to treatment in hyperlipidemic patients with diabetes were higher than levels in healthy controls (10.4 +/- 1.9 vs. 3.1 +/- 0.4 U/ml, p < 0.0001), and adiponectin levels were lower than controls (3.20 +/- 0.49 vs. 5.98 +/- 0.42 microg/ml, p < 0.0001). PDMP decreased significantly in group B (before vs. 6M, 10.6 +/- 2.0 vs. 8.0 +/- 1.7 U/ml, p < 0.01), but not in group A (before vs. 6M, 9.4 +/- 1.9 vs. 9.6 +/- 1.7 U/ml, not significant). In contrast, group A exhibited a significant increase in adiponectin levels after treatment (before vs. 6M, 3.29 +/- 0.51 vs. 4.16 +/- 0.60 microg/ml, p < 0.001). Furthermore, group C exhibited significant improvement in both PDMP and adiponectin levels after treatment (PDMP, before vs. 6M, 11.2 +/- 2.0 vs. 4.5 +/- 2.7 U/ml, p < 0.001; adiponectin, before vs. 6M, 3.24 +/- 0.41 vs. 4.02 +/- 0.70 microg/ml, p < 0.001). Reductions of PDMP in combined therapy were significantly greater than those observed with EPA alone (p < 0.05 by ANOVA). In addition, soluble CD40 ligand exhibited almost the same change as PDMP in all therapy groups. These results suggest that pitavastatin possesses an adiponectin-dependent antiatherosclerotic effect, and this drug is able to enhance the anti-platelet effect of EPA. The combination therapy of pitavastatin and EPA may be beneficial for the prevention of vascular complication in hyperlipidemic patients with type II diabetes.
authors.affiliation: Division of Hematology, Kishiwada City Hospital, Kishiwada, Japan. shosaku-n@mbp.ocn.ne.jp
authors.forename: Shosaku
authors.initials: S
authors.lastname: Nomura
authors.forename: Norihito
authors.initials: N
authors.lastname: Inami
authors.forename: Akira
authors.initials: A
authors.lastname: Shouzu
authors.forename: Seitarou
authors.initials: S
authors.lastname: Omoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kimura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanaka
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Urase
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohtani
authors.forename: Toshiji
authors.initials: T
authors.lastname: Iwasaka
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000367:Age Factors; D000368:Aged; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D004359:Drug Therapy, Combination; D019040:E-Selectin / Q000097:blood; D015118:Eicosapentaenoic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D012737:Sex Factors
chemical_list: D052242:Adiponectin; D023201:CD40 Ligand; D002784:Cholesterol; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019040:E-Selectin; D015118:Eicosapentaenoic Acid; D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; C517652:hemoglobin A1c protein, human; C108475:pitavastatin