PS 02-48 RELATIONSHIP BETWEEN MATRIX METALLOPROTEINASES WITH CARDIAC STRUCTURAL AND FUNCTIONAL IMPAIRMENTS IN PATIENTS WITH RESISTANT HYPERTENSION AND TYPE 2 DIABETES MELLITUS

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Abstract

Objective:

We aimed to investigate the relationship between plasma concentrations of matrix metalloproteinases (MMP), their tissue inhibitors and cardiac diastolic function and structural changes in the heart in patients with resistant hypertension (RH) and type 2 diabetes mellitus (DM).

Design and Method:

Eighteen patients with RH and type 2 DM (43–72 years old, mean aged 58.6 ± 7.5 years, 6 male, office blood pressure (BP) 174.4 ± 20.2/94.1 ± 15.2mmHg, 24-h BP- 161.5 ± 18.2/84.0 ± 13.0 mmHg, basal glycaemia 8.8 ± 2.3 mmol/L, HbA1c 6.8 ± 0.7%) were studied through measurement of office and 24-h BP, echocardiography (evaluation of left ventricular mass index (LVMI) (Devereux formula) and left ventricular (LV) diastolic function (mitral flow early (E) and late (A) phase ratio (E/A), isovolumetric relaxation time (IVRT)) and laboratory tests (HbA1c and basal glycaemia levels, plasma concentrations of MMP-9, MMP-2, tissue inhibitor of MMP type 1 (TIMP1), TIMP-1/MMP-2 and TIMP-1/MMP-9 ratios). On average, patients were taking 4 (3–5) antihypertensive drugs.

Results:

According to correlation analysis decreased MMP-2 concentration was associated with increased both linear anteroposterior left atrium diameter and LV end-diastolic dimension (R = −0.64, P = 0.032 and R = −0.76, P = 0.006, respectively). Besides this, elevated TIMP-1 concentration and TIMP-1/MMP-2 ratio was linearly associated with growth of LVMI (R = 0.55, P = 0.018 and R = 0.69, P = 0.018, respectively), increased IVRT (R = 0.76, P = 0.006 and R = 0.87, P = 0.000) and decreased E/A ratio (R = −0.61, P = 0.048 and R = −0.68, P = 0.02). The HbA1c level was negatively correlated with MMP-2 (R = −0.54, P = 0.038) and positively correlated with TIMP-1/MMP-2 ratio (R = 0.59, P = 0.018).

Conclusions:

In patients with RH and DM type 2 the decrease in MMP-2 activity is accompanied by expansion of the left heart chambers, while the increase of TIMP-1 level and TIMP-1/MMP-2 ratio are associated with LV hypertrophy and diastolic dysfunction that confirms the role of fibrosis in their development. The decrease in MMP-2 activity and also the imbalance between MMP-2 and its inhibitors in favor of TIMP-1 depend on degree of glucose metabolism disorder.

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