Isoflavones and the Coronary Circulation in Men and Women With Coronary Artery Disease

Phase 2

Completed

Brief Summary: The aim of this study is to investigate the effect of genistein administration on coronary arteries in humans. We will measure the size of a coronary artery and the speed and amount of blood flow in response after subjects have ingested Supro® drinks (a soy protein drink containing genistein).

Recruitment & Eligibility

Inclusion Criteria

Aged 30-75 years
Patients requiring diagnostic coronary angiography
Presence of coronary artery disease on angiogram but with at least one non-obstructed (lesions <70% narrowed compared with the adjacent normal part of the vessel) atheromatous vessel (confirmed at diagnostic cardiac catheterisation)
Female patients must be postmenopausal (FSH>40 IU/L)
Willing to give informed, written consent

Exclusion Criteria

Age <30 or >75 years
Allergy to radiographic contrast media
Sino-atrial disease or significant bradycardia
Concomitant medication with persantin (dipyridamole) or theophyllines
Asthma
Hypertension
Left ventricular hypertrophy or dysfunction (clinical/ECG/echo/CXR)
Female patients with FSH<40 IU/L (postmenopausal)
Female patients currently taking hormone therapy, or who have taken hormone therapy in previous 6 months
Unwilling to give written informed consent
Participation in another study within previous 60 days

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Drink identical to Supro but containing no genistein, once daily for 3 days
Genistein	Genistein	Supro drink once daily for 3 days

Primary Outcome Measures

Name	Time	Method
Coronary Blood Flow	Day 3-4 after Supro/placebo started.	Measurement of diameter 4mm distal to the Doppler wire tip (measured using quantitative coronary angiography) and blood flow velocity, measured using intracoronary Doppler), were made at baseline and at peak velocity change. A quantitative estimate of coronary blood flow was calculated from the Doppler flow velocity and quantitative angiographic data using the following equation: Q = 3.14(D2/4)(APV/2)(0.6) where Q is flow (ml/min), D is vessel diameter (mm) and APV is average peak velocity (cm/s). Data below are measurements taken at peak blood flow response following an infusion of acetylcholine (10-5M).
Coronary Artery Diameter	Day 3-4 after Supro/placebo started.	Coronary angiograms were acquired digitally using a real-time digital image acquisition system (Siemens AG, Berlin and Munich, Germany) and analysed off-line using quantitative coronary angiography (MEDIS, Leiden, The Netherlands). Basal luminal diameter of the entire coronary artery (mean luminal diameter) was measured for all subjects. Mean luminal diameter and luminal diameter approximately 4 mm distal to the tip of the Doppler wire were measured. The latter measurements were used to quantify volume flow as described previously. Data below are mean coronary artery diameter response following infusion of acetylcholine (ACh 10-5 M).

Secondary Outcome Measures

Name	Time	Method
Serum Genistein Concentrations	Day 3 after Supro/placebo started.	Measured from serum using liquid-chromatographic tandem mass spectrometric bioanalytical assays (HFL Ltd, Fordham, Cambridgeshire, UK).