Effects of Valsartan on Inflammatory and Oxidative Stress Markers in Hypertensive, Hyperglycemic Patients: An Open-Label, Prospective Study

Abstract Background: Diabetes mellitus and hypertension are aggravated by activation of the renin-angiotensin system caused by increased oxygen stress and local inflammatory responses. Several studies have suggested that angiotensin II type 1 receptors can reduce inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin [IL]-6, IL-18, soluble vascular cell adhesion molecule [VCAM]-I, and l -selectin) and oxidative stress markers (urinary 8-hydroxy-7,8-dihydro-2'-deoxyguanosine [8-OHdG] and 8-epi-prostaglandin F2α [8-isoprostane]) in hypertensive patients. Objective: The aim of this study was to assess the effects of valsartan, an angiotensin II receptor blocker, on inflammatory and oxidative stress markers in hypertensive patients with mild diabetes or impaired glucose tolerance. Methods: In this open-label, prospective study, hypertensive patients aged >20 years with mild diabetes (requiring treatment by diet alone or an oral hypoglycemic), seen on an outpatient basis at the Division of Diabetes, Metabolism, and Endocrinology, Omori Hospital, Toyko, Japan, who were receiving a therapeutic dietary regimen for ≥1 month in the treatment of diabetes or hypertension, were eligible for enrollment. Blood pressure, inflammatory markers (hs-CRP, IL-6, IL-18, VCAM-1, and L -selectin), and oxidative stress markers (urinary 8-OHdG and 8-isoprostane) were monitored before treatment commencement with valsartan (40-80 mg/d) and after 3 months of treatment. Results: A total of 26 patients (18 men, 8 women; mean [SD] age, 57.7 [11.3] years; mean [SD] weight, 65.3 [13.1] kg) were enrolled in the study. After 3 months of treatment, patients' mean (SD) blood pressure had significantly decreased from 153.1 (11.2)/88.3 (11.4) to 143.7 (13.7)/85.2 (9.0) mm Hg ( P < 0.05). Among the inflammatory and oxidative stress markers, hs-CRP, VCAM-1, and urinary 8-OHdG concentrations decreased significantly from 0.231 (0.199) to 0.134 (0.111) mg/dL ( P = 0.043), 471.1 (193.9) to 403.2 (135.2) ng/mL ( P = 0.012), and 12.12 (5.99) to 8.07 (3.36) ng/mg · creatinine ( P = 0.001), respectively. The reductions in these markers were observed in patients regardless of whether or not their glycosylated hemoglobin (HbA1c ) concentration improved (defined as a decrease of ≥1% in HbA1c ). Conclusion: This small, open-label, prospective study found that a 3-month treatment with valsartan was associated with a significant reduction of hs-CRP, VCAM-1, and urinary 8-OHdG concentrati