title: Effects of candesartan in hypertensive patients with type 2 diabetes mellitus on inflammatory parameters and their relationship to pulse pressure.
abstract: BACKGROUND
  Angiotensin receptor blockers (ARBs) are reported to provide direct protection to many organs by controlling inflammation and decreasing oxidant stress in patients without arteriosclerosis. This study aimed to evaluate (1) whether an ARB (candesartan) decreases values for inflammatory parameters in hypertensive patients with type 2 diabetes mellitus of long duration accompanied by arteriosclerosis and (2) whether there any predictors of which patients would receive the benefits of organ protection by candesartan.
  
  
  METHODS
  We administered candesartan therapy (12 mg daily) for 6 months and evaluated whether there was improvement in serum inflammatory parameters high molecular weight adiponectin (HMW-ADN), plasminogen activator inhibitor-1 (PAI-1), highly sensitive C-reactive protein (Hs-CRP), vascular cell adhesion molecule-1 (VCAM-1) in serum and urinary-8-hydroxydeoxyguanosine (U-8-OHdG). We then analyzed the relationship between the degree of lowering of blood pressure and inflammatory factors and the relationship between pulse pressure and inflammatory factors. Finally, we analyzed predictive factors in patients who received the protective benefit of candesartan.
  
  
  RESULTS
  After 6 months of treatment, significant improvements from baseline values were observed in all patients in HMW-ADN and PAI-1 but not in Hs-CRP, VCAM-1 and U-8-OHdG. Multilinear regression analysis was performed to determine which factors could best predict changes in HMW-ADN and PAI-1. Changes in blood pressure were not significant predictors of changes in metabolic factors in all patients. We found that the group with baseline pulse pressure <60 mmHg had improved HMW-ADN and PAI-1 values compared with the group with baseline pulse pressure ≥ 60 mmHg. These results suggest that pulse pressure at baseline could be predictive of changes in HMW-ADN and PAI-1.
  
  
  CONCLUSIONS
  Candesartan improved inflammatory parameters (HMW-ADN and PAI-1) in hypertensive patients with type 2 diabetes mellitus of long duration independent of blood pressure changes. Patients with pulse pressure <60 mmHg might receive protective benefits by candesartan.
  
  
  BACKGROUND
  UMIN000007921.
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Minato-ku, Tokyo, Japan. m-sakamoto@umin.ac.jp
authors.forename: Masaya
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Iuchi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Isaka
authors.forename: Noriko
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kayama
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Tojo
authors.forename: Michihiro
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Kazunori
authors.initials: K
authors.lastname: Utsunomiya
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D002097:C-Reactive Protein / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood*; D007564:Japan; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011446:Prospective Studies; D013777:Tetrazoles / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D018836:Inflammation Mediators; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D013777:Tetrazoles; D019010:Vascular Cell Adhesion Molecule-1; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002097:C-Reactive Protein; D003849:Deoxyguanosine; C081643:candesartan