To determine if there is a relationship between coronary flow reserve (CFR) and platelet/plasma BH2 and BH4 levels in patients with high cardiovascular risk .

Primary parameter :

relationship between coronary flow reserve (CFR) and platelet/plasma BH2 and BH4 levels in patients with hypertension and concomitant cardiovascular risk factors.

Secondary parameter:

Levels of cGMP in platelets.

4. Study design

Three parallel groups of patients (n=15 per group):

• Group 1 with normal coronary flow reserve (CFR ≥2.5)

• Group 2 with reduced coronary flow reserve (CFR≤2.0)

  o Group 3 control subjects (without a high risk profile according to ESC score chart http://www.heartscore.org. ) matched for age (between 40 and 80 years of age)

• and gender. 1/3 enrolled patients must be diabetic (Type2 diabetes)

Inclusion Criteria:

• o men and women (females of childbearing potential must be using highly effective contraceptive precautions such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence or vasectomised partner)

  • Females of childbearing potential or within two years from the menopause must have a negative urine pregnancy test
  • between 40 and 80 years of age
  • documented history of hypertension
  • smokers/non smokers R
  • type 2 diabetes R
  • Moderate to severe kidney disease (GFR >30 and <60 ml/min/1.73m2 (estimated MDRD) R
  • Hypercholesterolemia R
  • Receiving an optimal standard antihypertensive treatment for at least 6 months, stable for at least 15 days
  • All other concomitant treatments stabilized at least for the preceding 15 days
  • Able to give written informed consent

Exclusion Criteria:

• o Females of childbearing potential not using highly effective contraceptive precautions

  • Patients with obstructive (>50% diameter reduction) CAD on the LAD (based on invasive angiography or coronary CTA) or with evidence of previous myocardial infarction or history of revascularization in the LAD territory.
  • CAD on the RCA or CX with diameter reduction > 50% (based on invasive angiography or coronary CTA) , either native or revascularized (stent)
  • Patients with infectious disease and/or chronic inflammatory diseases
  • Epicardial coronary arteries spasm
  • Patients with severe valve disease and/or significant left ventricular wall motion abnormalities
  • Patients under treatment with non-selective beta blockers including propranolol, nadolol, pindolol, labetalol, penbutolol, sotalol, carvedilol, and timolol.
  • Contraindications to dipyridamole infusion: asthma, bronchospasm, previous < 24 hours ingestion of phylline derivatives (tea, coffee, cola, xanthines and chocolate) sick sinus syndrome, advanced AV block (second and third degree), systolic blood pressure < 90 mmHg, cerebral ischemia, severe sinus bradycardia (heart rate <40/min), use of dipyridamole during the last 24 h, severe atherosclerotic lesions of extracranial artery >75%.
  • Acute treatment or treatment for acute diseases
  • Patients receiving steroidal anti-inflammatory drugs, dietary supplements of folic acid, or antioxidant vitamins.
  • Any condition that may prevent the pt to give informed consent , enter the study or bias the results.
  • Participating into other studies

Symptomatic (angina symptoms both typical and atypical ) patients referred to the hospital with hypertension plus risk factors: diabetes, hypercholesterolemia, smoking, chronic renal failure