Effects Of Angiotensin Ii Receptor Blocker (Arb) And Ppar-Gamma Agonist On Vascular Failure In Patients With Hypertension, Diabetic Mellitus And Chronic Kidney Disease

Background: Hypertension (HT), diabetes mellitus (DM), and chronic kidney disease (CKD) are known to be associated with “vascular failure”, which is defined as the integration of endothelial dysfunction and metabolic abnormalities of the vessel wall including inflammation, oxidative stress. We evaluated effects of ARB, calcium channel blocker (CCB), and PPAR-γ agonist on vascular failure in patients with HT, DM and CKD. Methods: Forty eight patients with untreated HT, type 2 DM (HbA1c 6.0 – 6.5%), and CKD (stage 3 or 4) were randomized to receive telmisartan ( Tel. group , n=12), telmisartan and pioglitazone ( Tel. and Pio. group , n=12), amlodipine ( Aml. group , n=12), or amlodipine and pioglitazone ( Aml. and Pio. group , n=12). We measured flow-mediated dilatation (FMD) and nitroglycerin-induced dilatation (NID) of brachial artery, and pulse wave velocity (PWV). We also measured high sensitivity C-reactive peptide (hsCRP) and TBARS levels as indexes of inflammation and oxidative stress. Measurements were performed at baseline, and then at every 6 months after the treatments. Results: Blood pressure was significantly decreased in these groups, and there was no difference among four groups at baseline and during the study. FMD was significantly increased, and PWV, hsCRP, and TBARS were significantly decreased in four groups. However, these improvements were much better in the Tel. and Pio. group than the other groups. NID did not change during the study. Conclusion: Combination therapy with ARB and PPAR-γ agonist was much better in the improvement of vascular failure in patients with HT, DM and CKD as compared with the therapy with ARB alone, CCB alone, or CCB and PPAR-γ agonist.