Free accessResearch articleFirst published online 2011-7
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
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.
Methods and 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/m2, 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 metalloproteinase-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.
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