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