Clinical trial NCT03841383: Association Between Coronary Flow Reserve and BH4 Levels in High CV Risk
Official title: Study to Investigate the Association Between Coronary Flow Reserve and BH4 Levels in Patients With High Cardiovascular Risk
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypertension,Essential
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: Servier
First posted: 2019-02-15
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Symptomatic (angina symptoms both typical and atypical ) patients referred to the hospital with hypertension plus risk factors: diabetes, hypercholesterolemia, smoking, chronic renal failure

Brief summary: 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 .

Detailed description: 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)

Eligibility criteria: 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

Primary outcomes:
measure: BH2 and BH4 levels (ng/ml) in plasma and platelets
timeFrame: 1 week
measure: Coronary Flow Reserve (CFR) Trans Thoracic Doppler Echocardiography
timeFrame: 1 week
measure: Relationship between coronary flow reserve (CFR) and platelet/plasma BH2 and BH4 levels.
timeFrame: 1 week
Secondary outcomes:
measure: Levels of cGMP in platelets
timeFrame: 1 week
Other outcomes:
Locations:
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
Study officials:
affiliation: IRCCS Ospedale San Raffaele
name: Paolo G Camici, MD
role: PRINCIPAL_INVESTIGATOR
References: