The Impact of Caffeine on Brachial Endothelial Function in Healthy Subjects and in Patients With Ischemic Heart Disease

Study Overview
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Brief Summary
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Prior work (Chris, M. et al, Clinical Science 2005; 109, 55-60) has demonstrated that drinking a cup of coffee (80-100 mg of caffeine) an hour before endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery, effects endothelial function in healthy adults subjects. This effect might be attributed to caffeine, given that decaffeinated coffee (<2 mg of caffeine) was not associated with any change in endothelial performance. In the current study we intend to further examine the impact of caffeine on brachial endothelial function among healthy subjects & in patients with proven ischemic heart disease.

Detailed Description
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Background: Prior work (Chris, M. et al, Clinical Science 2005; 109, 55-60) has demonstrated that drinking a cup of coffee (80-100 mg of caffeine) an hour before endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery, effects endothelial function in healthy adults subjects. This effect might be attributed to caffeine, given that decaffeinated coffee (<2 mg of caffeine) was not associated with any change in endothelial performance. In the current study we intend to further examine the impact of caffeine on brachial endothelial function among healthy subjects & in patients with proven ischemic heart disease. Aim: To evaluate the impact of 200 mg caffeine tablet intake (equivalent to 2 cups of coffee), compared to placebo on brachial endothelial function in healthy subjects & in patients with proven ischemic heart disease. Methods: Patients will be invited for two endothelial function tests 1 week apart. ECG, heart rate & blood pressure will be recorded at rest prior to each test. Following overnight fasting and discontinuation of all medications for ≥ 12 hours and absence of > 48 hour caffeine consumption, patients will receive 200 mg of caffeine tablets or placebo, in a double-blind, cross-over study design. An hour later the patient will undergo endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent, nitroglycerin (NTG)-mediated vasodilation will be assessed non-invasively in the brachial artery, using a high resolution (15 MHz) linear array ultrasound. Prior to and after the FMD, blood will be drawn to test caffeine levels, adiponectin, CBC, electrolytes, CRP and lipids.

Official Title
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The Impact of Caffeine on Brachial Endothelial Function in Healthy Subjects & in Patients With Ischemic Heart Disease

Conditions
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Coronary Disease

Intervention / Treatment
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* Drug: Caffeine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with documented ischemic heart disease Healthy subjects who are not heavy regular coffee drinkers Exclusion Criteria: Patients with unstable angina pectoris Patients with acute or chronic heart failure Patients with cardiac arrhythmia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAD patients<br>Patients with prior history of coronary artery disease (CAD) (myocardial infarction, cerebrovascular accident, coronary angioplasty, S/p CABG operation) who will be given on the first day either caffeine of placebo tablet and 1-2 hours thereafter a brachial artery endothelial function testing (BRT) will be assessed for measuring the FMD. After 1 week the patients will come for a second BRT on placebo/caffeine tablets. If the patient received caffeine tablet the first BRT, he will be receiving placebo tablet the second week, however, if the patient received placebo the first BRT, a caffeine tablet will be given prior to the second BRT. | Drug: Caffeine<br>* Caffeine 200 mg tablet<br>|
| Experimental: Placebo<br>Patients with prior history of coronary artery disease (CAD) (myocardial infarction, cerebrovascular accident, coronary angioplasty, S/p CABG operation) who will be given on the first day either caffeine of placebo tablet and 1-2 hours thereafter a brachial artery endothelial function testing (BRT) will be assessed for measuring the FMD. After 1 week the patients will come for a second BRT on placebo/caffeine tablets. If the patient received caffeine tablet the first BRT, he will be receiving placebo tablet the second week, however, if the patient received placebo the first BRT, a caffeine tablet will be given prior to the second BRT. | Drug: Placebo<br>* Placebo pills<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow-mediated dilation (FMD) as surrogate of brachial artery endothelial function |  | 1-2 hours post caffeine (or placebo) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Markers of inflammation such as hs-CRP, Il6, homocysteine, serum caffeine level |  | 1-2 hours post caffeine or placebo | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronary disease, atherosclerosis, endothelial function, caffeine, cerebrovascular disease, prevention