This is a pharmacogenomic prospective , four-arms, parallel groups, active comparator controlled study in essential hypertensive patients never treated before.

Each patient will be genotyped for SNPs (single nucleotide polymorphism) in preliminary genetic profiles and will be treated according to their genetic profile with Peri (Perindopril) 4 mg or HCTZ ( hydrochlorothiazide) 12.5 mg.

At screening visit each patient will be genotyped for SNPs in preliminary genetic profiles with a custom SNP array.

The therapy scheme includes 2-4-week run-in period after which eligible patients will be treated according to their genetic profile with Peri 4 mg or HCTZ 12.5 mg. Titration to Peri 8 mg or HCTZ 25 mg could be possible after one month treatment.

Patients without any genetic profile will be randomly assigned to HCTZ or Peri treatment as control groups.

The treatment period will last 8 weeks, while the study about 10-12 weeks

Four cases may occur:

• patient with HCTZ profile, HCTZ treatment;
• patient with Peri profile, Peri treatment;
• patient without HCTZ nor Peri profile, randomization for HCTZ or Peri;
• patient with both profiles, treatment according to the profile with the higher number of positive contributors.

Eligible patients will be treated according to their genetic profile with Peri 4 mg or HCTZ 12.5 mg/die.

Titration to Peri 8 mg or HCTZ 25 mg could be possible after 4 weeks treatment. The treatment period will last 8 weeks, while the study about 10-12 weeks

Inclusion Criteria:

• Male/Female patients aged 25-60 years.

• Naive hypertensive patients (newly diagnosed, never treated before).

• Documented mild to moderate arterial hypertension, as defined below:

  1. At Visits 1 and 2 (week -4 and week -2 run-in period) the mean of the last 3 consecutive readings of office SBP must be >= 140 mmHg and/or DBP must be >=90 mmHg, when measured by office blood pressure (OBP);
  2. At Visit 3 (week 0) enrolment , the mean of the last 3 consecutive readings of SBP must be >= 140 mmHg and <160 mmHg, and DBP must be >= 90 mmHg and <110 mmHg, when measured by OBP.

• Signed informed consent for genotyping.

Exclusion Criteria:

• known causes of secondary hypertension;
• pregnant, nursing women or women of childbearing potential taking anti-contraceptive medication;
• severe or malignant hypertension;
• history of renal artery disease;
• significant renal disease (estimated creatinine clearance less than 60 mL/min);
• hepatic disease;
• cardiac diseases (myocardial infarction, atrial fibrillation, etc);
• diabetes (fasting plasma glucose >125mg/dL);
• statin treatment;
• obesity (BMI>30 kg/m2).