ARTERIAL STIFFNESS IMPROVEMENT IN HYPERTENSIVE TYPE 2 DIABETIC PATIENTS: DISSIMILAR EFFECTS OF CANAGLIFLOZIN AND PERINDOPRIL

Abstract

Objective: We have shown in hypertensive type 2 diabetic patients (DM) a strong correlation between serum uric acid (SUA) and pulse wave velocity (PWV). Additionally, after 6 months treatment, we found a significant PWV improvement either with perindopril or canagliflozin that, when adjusted for office BP values, the PWV improvement was blunted in the perindopril treated patients while in those receiving canagliflozin a significant effect still remains. Thus, the aim of the present work was to evaluate in normoglycemic diabetic hypertensive patients with normal renal function, the effects and relationships of canagliflozin and perindopril on SUA, 24hs AMBP and carotid femoral PWV. Design and method: For 6 month, 40 hypertensive DM patients, under metformin 2000 mg and amlodipine, received canagliflozin 100–300 mg 10 mg daily (n = 20, 10 females, 59 ± 4y) while other 20 patients (8 females, 62 ± 4y) received perindopril 10 mg on top. Laboratory parameters determined at baseline and after a 6-month treatment were: HbA1C, fasting blood glucose level, glomerular filtration rate, SUA, urine acid uric, 24 h ambulatory blood pressure monitoring (ABPM) and PWV. Results: After 6 months treatment with canagliflozin, a decrease in PWV, (12.29 ± 0.16 to 8.49 ± 0.09m/sec; p < 0.001), HbA1C (8.1 to 7.0%; p < 0.05), SUA (7.87 ± 0.06 to 6.83 ± 0.06 mg/%; p < 0.05), and 24 h ABPM (154 ± 6/96 ± 5 to 141 ± 3/86 ± 4mmHg; p < 0.01) was observed. Similarly, after Perindopril, a decrease in 24hs ABPM (152 ± 7/98 ± 7 to 139 ± 6/84 ± 5mmHg; p < 0.05), PWV (12.53 ± 0.15 to 8.92 ± 0.19m/sec; p < 0.001) and SUA (7.77 ± 0.18 to 7.35 ± 0.11mg%; p < 0.05) was observed. Nevertheless, the SUA reduction induced by canagliflozin (-13.20 ± 0.71%) was greater (p < 0.001) than the induced by Perindopril (-4.98 ± 1.30%). A significant correlation between delta SUA and delta PWV was only observed with canagliflozin (r: 0.82, p < 0.001). Urine uric acid increased from 350 ± 20 to 580 ± 30 mg/24hs (p < 0.05) with canagliflozin, whereas no changes were observed with perindopril. Conclusions: In patients with type 2 DM and hypertension, both canagliflozin and perindopril were able to ameliorate blood pressure and arterial stiffness values. Moreover, canagliflozin improved PWV associated to uric acid reduction. It is suggested that the reduction in SUA and the increase in UA urine excretion seems to have an intrinsic vascular wall effect therefore, it may reduce cardiovascular risk.