Association Between Coronary Flow Reserve and BH4 Levels in High CV Risk

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