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Objectives. To assess the effects of two types of diuretics (indapamide and HCTZ) added to an ACE-inhibitor on ventriculo-arterial coupling (endothelial and arterial function, left ventricular - LV function, and biomarkers) in patients with hypertension and diabetes with normal ejection fraction (EF).Methods: This is a prospective, randomised, parallel, active-controlled, PROBE design study in 56 patients (57±9 years, 51% men) with mild-to-moderate arterial hypertension (diagnosed by ABPM) and type 2 diabetes, with normal EF, randomized 1:1 to either indapamide (1.5 mg SR) or HCTZ (25 mg), added to quinapril (10-40 mg/day); all patients had conventional, tissue Doppler, and speckle tracking echocardiography, assessment of endothelial (FMD) and arterial functions, ventriculo-arterial coupling, and biomarkers, at baseline and after 6 months.Results: Baseline characteristics were similar between groups; systolic and diastolic blood pressure, decreased similarly, by 15% and 9%, respectively, on indapamide, and by 17% and 10%, respectively, on HCTZ (all p<0.05). Mean longitudinal systolic velocity and longitudinal strain improved by 7% and 14% on indapamide (from 5.6±1.0 to 6.0±1.0 cm/s, and from 16.2±3.5 to 18.5±3.5%, both p<0.05), but decreased on HCTZ (p<0.05 for intergroup differences), while EF and radial systolic velocities did not change. Similarly, mean longitudinal early diastolic velocity and flow propagation velocity improved by 13% and 31% on indapamide (from 6.0±1.6 to 6.8±1.5 cm/s, and from 48±7 to 63±11 cm/s, both p<0.05), but were not changed on HCTZ (p<0.05 for intergroup differences). These were associated with improved endothelial (FMD increased by 19% and microalbuminuria decreased by 30%) and arterial functions (pulse wave velocity decreased by 4%) on indapamide, but not on HCTZ.Conclusion: Indapamide improves endothelial and arterial function, and increases longitudinal LV function by comparison with HCTZ, in patients with mild-to-moderate hypertension and diabetes, after 6 months. This is the first study proving that thizide-like diuretics have important vascular effects, which can improve ventriculo-arterial coupling.