There are evidences of the important role of decreased activity of matrix metalloproteinases (MMP) in the pathophysiology of hypertension through an increase in arterial stiffness. The aim of study is to define the role of MMP and their inhibitors in prediction of renal denervation (RD) efficacy in patients with resistant hypertension (RH) in the presence of type 2 diabetes mellitus (DM) or its absence.Design and Method:
We studied 36 patients with RH (11 men; mean age 53.8 ± 7.6 years, mean office BP: 171.6 ± 20.0/98.5 ± 14.4 mmHg, mean 24-h BP: 161.9 ± 20.9/90.4 ± 16.1 mmHg) who underwent RD and completed 6-month follow-up evaluations, including office and 24-hours ambulatory blood pressure (BP) measurements and laboratory tests (HbА1c and basal glycaemia levels, plasma concentrations of MMP-9, MMP-2, tissue inhibitor of MMP-1 (TIMP-1). Patients were then divided into 2 groups: those with DM (n = 14, mean HbA1c 6.8 ± 0.7%, mean level of basal glycaemia 8.3 ± 2.0 mmol/L) and those without (n = 22). Antihypertensive and antidiabetic treatments were not changed during the 6 months of follow-up.Results:
There were no differences between groups regarding age, sex, concentrations of plasma of matrix metalloproteinases, TIMP-1 and TIMP-1/MMP ratios, office, and 24-hour ABPM levels. However, pulse pressure in diabetic patients was significantly higher than in patients without DM (76.3 ± 12.8 vs. 66.7 ± 13.1 mmHg, P = 0.036). The numbers of responders (with office systolic BP (SBP) reduction ≥10 mmHg) in groups without DM and with it were comparable (16 (72%) and 8 (57%), p = 0.33). Among patients without DM in nonresponders (with SBP reduction <10 mmHg) the concentration of TIMP-1 was significantly higher than that in responders (699.8 (637.4–918.2) vs. 607.9 (534.9–649.3) ng/ml, accordingly, P = 0.02), while similar differences between responders and nonresponders among diabetic patients were not observed.Conclusions:
The association between increased activity of TIMP-1 and decreased efficacy of RD was demonstrated only for patients with RH without DM, reflecting the more complex mechanisms of increase of arterial stiffness and BP in diabetic patients.