title: Effect of pioglitazone and ramipril on biomarkers of low-grade inflammation and vascular function in nondiabetic patients with increased cardiovascular risk and an activated inflammation: results from the PIOace study.
abstract: OBJECTIVE
  This study investigated the effects of pioglitazone (PIO), ramipril (RAM), or their combination (PIRA) on low-grade inflammation in nondiabetic hypertensive patients with increased cardiovascular risk.
  
  
  RESULTS
  Patients enrolled in this placebo-controlled, double-blind, randomized, parallel trial (72 male, 77 female, aged 60 ± 9 years, body mass index 30.4 ± 4.7 kg/m(2), duration of hypertension 9 ± 8 years) were treated with either 30/45 mg PIO (dose titration), 2.5/5 mg RAM, or their combination for 12 weeks. A reduction in high-sensitivity C-reactive protein was observed with PIO (-0.89 ± 1.98 mg/liter; -25%) and PIRA (-0.49 ± 2.11 mg/liter; -16%), while an increase was seen with RAM (0.58 ± 2.13 mg/liter; +20%, p < .05 vs PIO and PIRA). The 24-hour blood pressure profile showed a small increase with both monotherapies but a decrease with PIRA (p < .05 vs PIO). Improvements in biomarkers of chronic systemic inflammation and insulin resistance (IR) were observed in the PIO and PIRA arms only [PIO/RAM/PIRA: homeostasis model of assessment of IR: -0.78 ± 1.39 (-29%)/0.15 ± 1.03 (+5%)/ -1.44 ± 2.83 (-40%); adiponectin: 8.51 ± 5.91 (+104%)/ 0.09 ± 2.63 (+1%)/ 8.86 ± 6.37 mg/liter (+107%); matrix metallo-proteinase-9: -48 ± 127 (-12%)/-1 ± 224 (0%)/-60 ± 210 ng/ml (-13%), p < .05 for RAM vs PIO or PIRA in all cases].
  
  
  CONCLUSIONS
  Our 3-month study in nondiabetic hypertensive patients showed a decrease in biomarkers of IR and chronic systemic inflammation with the PIO monotherapy and the PIRA combination only, which may help to explain some findings in other cardiovascular outcome trials.
authors: IKFE-Institute for Clinical Research and Development, Mainz, Germany. andreasp@ikfe.de
authors: Andreas
authors: A
authors: Pfützner
authors: Markolf
authors: M
authors: Hanefeld
authors: Lida A
authors: LA
authors: Dekordi
authors: Jürgen
authors: J
authors: Müller
authors: Iris
authors: I
authors: Kleine
authors: Winfried
authors: W
authors: Fuchs
authors: Thomas
authors: T
authors: Forst
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood* / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D048909:Diabetes Complications / Q000097:blood / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000097:blood* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D010919:Placebos; D017257:Ramipril / Q000008:administration & dosage / Q000494:pharmacology*; D012307:Risk Factors; D012720:Severity of Illness Index; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D007004:Hypoglycemic Agents; D010919:Placebos; D045162:Thiazolidinediones; D017257:Ramipril; D000077205:Pioglitazone