A TElmisartan and AMlodipine STudy to Assess the cardiovascular PROTECTive effects as measured by endothelial dysfunction in hypertensive at risk patients beyond blood pressure

INTERVENTION: Trade Name: Micardis® 40 mg Tabletten Pharmaceutical Form: Tablet INN or Proposed INN: TELMISARTAN CAS Number: 144701‐48‐4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 80‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: Amlodipin HEXAL® 5 mg Tabletten Pharmaceutical Form: Tablet CAS Number: 111470‐99‐6 Other descriptive name: AMLODIPINE BESILATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Trade Name: Amlodipin HEXAL® 10 mg Tabletten Pharmaceutical Form: Tablet CAS Number: 111470‐99‐6 Other descriptive name: AMLODIPINE BESILATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ Trade Name: Olmetec® 40 mg Filmtabletten Pharmaceutical Form: Film‐coated tablet CAS Number: 144689‐63‐4 Other descriptive name: OLMESARTAN MEDOXOMIL Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 40‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: HCT HEXAL® 12.5 mg Filmtabletten Pharmaceutical Form: Tablet INN or Proposed INN: HYDROCHLOROTHIAZIDE CAS Number: 58‐93‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 12.5‐ Trade Name: Esidrix® 25 mg Tabletten Pharmaceutical Form: Tablet INN or Proposed INN: HYDROCHLOROTHIAZIDE CAS Number: 58‐93‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ CONDITION: ? Male and female, treated and treatment‐naive patients with uncontrolled hypertension (defined as 20/10 mmHg above target BP of <140/90 mmHg [<130/80 mmHg for renally impaired and/ or diabetics patients]) ? Male and female treated patients with controlled hypertension (defined as target BP < 140/90 mmHg [ < 130/80 mmHg for renally impaired and/ or diabetics patients]) ; MedDRA version: 13.1 Level: PT Classification code 10020772 Term: Hypertension System Organ Class: 10047065 ‐ Vascular disorders Therapeutic area: Diseases [C] ‐ Cardiovascular Diseases [C14] SECONDARY OUTCOME: Secondary end point(s): • Change in stiffness measurement and pulse wave velocity after 26 ; weeks of treatment compared to baseline ; • Change in plaque echogenicity as measured by grayscale median (GSM) of the carotid arteria after 26 weeks of treatment compared to baseline ; • Change in blood pressure control rates (i.e. <140/90 mmHg and <130/80 mmHg for diabetics and renally impaired patients) after 6, 12 and 26 weeks compared to baseline ; • Change in intima media echogenicity as measured by grayscale median ; (GSM) of the carotid arteria after 26 weeks of treatment compared to ; baseline ; • Type and amount of additional antihypertensive medication after 12 and 26 weeks compared to baseline ; • Change in additional functional and inflammatory biomarkers compared to baseline Timepoint(s) of evaluation of this end point: 26 weeks PRIMARY OUTCOME: Main Objective: ? To show superior effects of the combination Telmisartan and Amlodipine (T and A) vs Olmesartan and HCTZ (O and HCTZ) on endothelial dysfunction as measured by flow mediated dilation (FMD) in hypertensive at risk patients beyond BP (equal BP in both arms; target BP <140/90 mmHg (<130/80 mmHg for renally impaired and/ or diabetic patients) including response dependent add‐on of other antihypertensive) Primary end point(s): ? Change in endothelial function as measured by flow mediated dilatation (FMD) after 26 weeks of treatment compared to baseline; Secondary Objective: ? To investigate the effects of T and A vs O and HCTZ in reducing arterial stiffness (as measured by PWV and AI) and carotid atherosclerotic plaques. Timepoint(s) of evaluation of this end point: 26 weeks INCLUSION CRITERIA: ? Ability to provide written informed consent in accordance with Good Clinical Practice and local legislation. ? Age 35 years or older. ? Male and female, treated and treatment‐naive patients with uncontrolled hypertension (defined as 20/10 mmHg above target BP of <140/90 mmHg [<130/80 mmHg for renally impaired and/ or diabetics patients]) ? Male and female treated patients with controlled hypertension (defined as target BP < 140/90 mmHg [ < 130/80 mmHg for renally impaired and/ or diabetics patients]) ? > 3 CVRFs and/or metabolic syndrome and/or diabetes mellitus and/or endorgan damage (see 3.3.3) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 350 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 226