The EFFERVESCENT trial is designed to evaluate the effects of a specific ARB, called valsartan, on atherosclerosis. The investigators want to know if treatment with valsartan will increase the blood levels of markers responsible for repair of the vessel wall, reduce oxidation and inflammation, improve the function of the blood vessels, and arrest or slow down the progression of atherosclerosis over time.

Atherosclerosis or 'hardening of the arteries' is a process that ultimately leads to the development of heart attacks, strokes, poor circulation, and death. Millions of Americans are affected by this progressive disease of the arteries. Researchers have tried to understand the very complex processes that lead to hardening of the arteries. Part of this research has taught the investigators that there are specific molecules that can cause damage or injury to the vessel wall by increasing oxidation and inflammation which, in turn, leads to atherosclerosis. Other molecules and cells have been found that can actually repair the vessel wall.

Currently, the best treatment the investigators have for preventing or slowing atherosclerosis is to control the patients' risk factors such as high blood pressure, diabetes, or cholesterol levels using prevention and specific drugs. Angiotensin receptor blockers (ARBs) are a class of drugs that have been shown in clinical trials to have many beneficial effects in patients with high blood pressure, advanced heart diseases (such as after heart attack and heart failure), and diabetes. However, whether these drugs will also be useful in people with early signs of hardening of the arteries, measured as a thickening of the carotid (neck) arteries is unknown, and is the purpose of this study.

The EFFERVESCENT trial is designed to evaluate the effects of a specific ARB, called valsartan, on atherosclerosis. The investigators want to know if treatment with valsartan will increase the blood levels of markers responsible for repair of the vessel wall, reduce oxidation and inflammation, improve the function of the blood vessels, and arrest or slow down the progression of atherosclerosis over time.

In this study, the investigators will recruit subjects who have a hardening or thickening of their carotid arteries, one of the main blood vessels in the neck. People will be screened with ultrasound or sonar examination for this. Two-thirds of those eligible for participation will receive valsartan while the remaining one-third will receive a placebo pill. The investigators and subjects will be unaware of which drug is being given until the end of the study. The study will last for 2 years. Half of the individuals will also be treated with a statin drug (used for cholesterol reduction) and the remaining individuals will not be on a statin.

The investigators will measure carotid artery thickening with magnetic resonance imaging (MRI); forearm blood vessel function using ultrasound; and they will perform blood tests to measure oxidation and inflammation in the blood stream and circulation stem cells that are responsible for healing. These tests will be repeated at 3 months, 1 year and 2 years after starting treatment. The investigators will also collect blood for genotyping where the DNA will be stored for future analysis to study whether subjects' genotype alters their susceptibility to treatments. The investigators' hypothesis is that ARB treated individuals will have less oxidation and inflammation, higher levels of stem cells, and a slower progression of arterial thickening.

Finding an early treatment for atherosclerosis would hopefully prevent future strokes, heart attacks, and deaths leading to improved longevity and reduced medical expenditure.

Inclusion Criteria:

• > 0.65 mm intima-media thickness of the carotid artery measured by ultrasound
• Males aged 21-80 years or women without child bearing potential up to age 80
• Can be on concomitant therapy with aspirin, thiazide diuretics, calcium antagonists (for treatment of hypertension), or beta-receptor antagonists.
• May be on statin if on stable dose for at least 2 months before recruitment

Exclusion Criteria:

• Angiotensin-converting enzyme (ACE) inhibitor or ARB therapy in the previous 3 months.
• Initiation or change in dose of statin therapy within 2 months before the study
• Inability to return to Emory for follow-up blood drawing and MR imaging
• Age < 21 or > 80 years
• Premenopausal females with potential for pregnancy
• Current neoplasm
• Chronic renal failure [creatinine > 2.5 mg/dL]
• Diabetes with hemoglobin (Hb) A1c > 8.5
• Anticipated change in lipid lowering therapy
• Inability to give informed consent
• MR exclusion criteria
• Blood pressure > 140 mmHg systolic and > 90 mmHg diastolic
• Low-density lipoprotein (LDL) cholesterol level >130 mg/dl
• Acute coronary syndrome within 2 months
• Acute cerebrovascular accident within 2 months