Alcohol and Atherosclerosis Pilot Study

The feasibility of a long-term randomized trial of alcohol intake on clinical endpoints is
uncertain. One approach that could minimize the size and duration of such a randomized trial
would be to assess the effect of alcohol on progression of radiologically-defined
atherosclerosis.

We propose a proof-of-principle pilot study of the effect of longer-term alcohol intake on
atherosclerosis. We will recruit and randomize 40 participants aged 55 and older at high
risk for CHD to a six-month period of consumption of a single 150 ml glass per day of either
10% ethanol (approximating wine) or water. At baseline and after 6 months, we will assess
aortic atherosclerosis using magnetic resonance imaging. We will determine adherence in
several ways, including serum markers, dietary recalls, and measurement of unused beverage.
The primary outcomes in this feasibility study will be compliance with alcohol intake and
the two MRI examinations. As secondary outcomes, we will measure standard and novel
cardiovascular risk markers, including inflammatory markers and measures of glucose
metabolism. We will assess safety on a continual basis, including repeated testing of liver
enzymes and blood counts.

If successful, this pilot study will form the basis for a more definitive trial to determine
the effect of alcohol intake on progression of atherosclerosis, which could itself establish
the feasibility of even larger, longer-term studies of alcohol intake and occurrence of
cardiovascular events.

Inclusion Criteria:

- Diabetes

- Current Smoking

- Hypertension

- Family history of heart disease

- High LDL Cholesterol (>130 mg/dl)

- Low HDL CHolesterol (<40 mg/dl)

- Body Mass Index of 30 kg/m^2

- Waist circumference greater than 40 inches for men and 35 inches for women

- Report intake of at least one drink in the last month

- Post-menopause (if woman)

Exclusion Criteria:

- History of myocardial infarction (MI)/ heart attack within prior 6 months.

- Revascularization procedure (coronary, carotid, or peripheral)

- Stroke

- Claustrophobia

- Intolerance to previous MRI examinations

- Standard MRI contraindications (e.g. pacemaker, intra-auricular implants, or
intracranial clips)

- Weight over 350 pounds

- Active atrial fibrillation

- Reports intake of more than 7 drinks per week currently, has previous or current
history of alcohol abuse based on standard questionnaires, or who has consumed more
than 4 drinks in one day within the last 6 months.

- Intolerance or allergy to alcohol consumption (includes flushing)

- Allergy to aspartame, acesulfame, or artificial food coloring

- Any severe illness expected to cause death or profound disability within 6 months

- Evidence of depression (as measured based on a Center for Epidemiological Studies
Depression score of 16 or higher)

- History of chronic liver disease

- Personal history of breast or any gastrointestinal cancer, uncontrolled hypertension
(blood pressure greater than or equal to 180/110)

- Chronic renal failure on dialysis

- Current use of Metronidazole or Warfarin

- Use of benzodiazepines, barbiturates, and related sedative/ hypnotics 4 or more days
per week.

- Severe psychiatric illness

- Inability to speak English

- Lack of a working telephone