title: Effects of lipid-lowering treatment on circulating microparticles in patients with diabetes mellitus and chronic kidney disease.
abstract: Elevated levels of circulating microparticles (MPs) may contribute to the high cardiovascular risk in diabetes mellitus (DM) and chronic kidney disease (CKD). Therefore, we investigated the effects of lipid-lowering treatment (LLT) with simvastatin alone (S) or with ezetimibe (S+E) on MPs in DM patients with or without CKD.
  
  
  
  After a placebo run-in period, 18 DM patients with an estimated glomerular filtration rate (eGFR) of 15-59 mL/min (CKD stages 3-4) (DM-CKD) and 21 DM patients with eGFR >75 mL/min (DM-only) were treated with S and S+E in a randomized, double-blind, crossover study. MPs from platelets, monocytes and endothelial cells (PMPs, MMPs and EMPs), and their expression of phosphatidylserine (PS), P-selectin, CD40 ligand (CD40L) and tissue factor (TF) were measured by flow cytometry.
  
  
  
  At baseline, all types of MPs, except TF-positive MMPs, were elevated in DM-CKD compared with DM-only patients. All MPs, regardless of origin and phenotype, were inversely correlated with eGFR. S reduced the expression of P-selectin, TF and CD40L on PMPs and of TF on MMPs in both patient groups. S+E had no further effect. S also reduced total PS-positive procoagulant MPs, PMPs and MMPs in DM-CKD but not in DM-only patients.
  
  
  
  DM patients with CKD stages 3-4 had elevated PMPs, EMPs and MMPs compared with DM patients with normal GFR. Simvastatin reduced procoagulant MPs, MMPs and PMPs in DM-CKD patients, suggesting a beneficial reduction of hypercoagulability in this high-risk patient group. Differences between DM-CKD and DM-only patients were counteracted by LLT.
authors.affiliation: Department of Medicine Solna, Clinical Pharmacology Unit, Karolinska University Hospital, Karolinska Institutet, Solna, Stockholm, Sweden Division of Nephrology, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
authors.forename: Tora
authors.initials: T
authors.lastname: Almquist
authors.affiliation: Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden Department of Medicine Solna, Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, Solna, Stockholm, Sweden.
authors.forename: Fariborz
authors.initials: F
authors.lastname: Mobarrez
authors.affiliation: Division of Nephrology, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Jacobson
authors.affiliation: Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallén
authors.affiliation: Department of Medicine Solna, Clinical Pharmacology Unit, Karolinska University Hospital, Karolinska Institutet, Solna, Stockholm, Sweden.
authors.forename: Paul
authors.initials: P
authors.lastname: Hjemdahl
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D018592:Cross-Over Studies; D003920:Diabetes Mellitus / Q000097:blood*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications; D012307:Risk Factors; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D019007:P-Selectin; C546937:SELP protein, human; D019821:Simvastatin; D000069438:Ezetimibe
keywords: CKD; cardiovascular; diabetes mellitus; statins; thrombosis