The purpose of this study is to examine why age is a strong risk factor for developing atherosclerosis, and whether this may, in part, be due to the effects of age on blood vessels.

The prevalence, incidence, and severity of atherosclerotic disease all markedly increase with age. Basic experimental and observational data demonstrate that aging magnifies the pathologic and clinical consequences of established risk factors and is the most potent individual risk factor for coronary atherosclerosis and for adverse outcomes following an ischemic event (such as stroke). These findings suggest that normal aging alters the vascular substrate so as to promote the development and progression of atherosclerosis.

This study will non-invasively characterize vascular age and atherosclerotic burden in participants with "successful" aging (i.e. those with no or minimal evidence of coronary atherosclerotic disease), and those with premature, clinically evident coronary artery disease. Measures of vascular age and atherosclerotic burden will be repeated three years after the first assessment. By examining the impact of vascular age on the initial extent and the progression of atherosclerotic burden over a three-year period, the study will test the hypothesis that vascular age is an important determinant of the age associated increase in atherosclerotic disease.

Three groups of participants will be studied:

Group 1: Participants in the Baltimore Longitudinal Study of Aging (BLSA) without known coronary artery disease. The anticipated number is 330.

Group 2: Individuals outside of the BLSA without known coronary, cerebral, and peripheral artery disease and with coronary artery calcium scores on MDCT (Multislice Detector Computed Tomography) of zero or less than the 25th percentile expected based on their gender and age. The anticipated number is 60.

Group 3: Individuals outside of the BLSA with premature coronary disease defined as prior documented myocardial infarction or symptoms compatible with ischemia in association with catheterization documented coronary disease of > 70% in a major coronary artery in a man younger than 50 years or a woman younger than 60 years. The anticipated number is 60.

• Baltimore Longitudinal Study of Aging, NIA participants
• Individuals without known coronary, cerebral, and peripheral artery disease and with coronary artery calcium scores on MDCT of zero or less than the 25th percentile expected based on their gender and age
• Individuals who on a screening MDCT scan have a coronary artery calcium score which is greater than the 50th percentile for their age and gender or individuals with premature coronary disease defined as prior documented myocardial infarction or symptoms compatible with ischemia in association with catheterization documented coronary disease of > 70%

• Najjar SS, Scuteri A, Lakatta EG. Arterial aging: is it an immutable cardiovascular risk factor? Hypertension. 2005 Sep;46(3):454-62. Epub 2005 Aug 15.
• Lakatta EG. Cardiovascular aging research: the next horizons. J Am Geriatr Soc. 1999 May;47(5):613-25. Review. No abstract available.
• Vaitkevicius PV, Fleg JL, Engel JH, O'Connor FC, Wright JG, Lakatta LE, Yin FC, Lakatta EG. Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation. 1993 Oct;88(4 Pt 1):1456-62.
• Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998 May 12;97(18):1837-47.
• Grundy SM, Balady GJ, Criqui MH, Fletcher G, Greenland P, Hiratzka LF, Houston-Miller N, Kris-Etherton P, Krumholz HM, LaRosa J, Ockene IS, Pearson TA, Reed J, Washington R, Smith SC Jr. Primary prevention of coronary heart disease: guidance from Framingham: a statement for healthcare professionals from the AHA Task Force on Risk Reduction. American Heart Association. Circulation. 1998 May 12;97(18):1876-87. No abstract available.

Inclusion Criteria:

For all groups:

• Ages 30 years or older
• Ability and willingness to participate in the protocol and undergo vascular studies, magnetic resonance imaging (MRI) scans, and chest MDCT examinations

Group 2:

• Coronary artery calcium score of zero or less than 25th percentile of that expected based on age and gender

Group 3:

• Known coronary disease on the basis of prior documented myocardial infarction or typical ischemic symptoms and catheterization documented stenosis of > 70% in at least one major coronary artery
• If male, diagnosis was made under 50 years of age
• If female, diagnosis was made under 60 years of age.

Exclusion Criteria:

• Atrial fibrillation
• For the first 2 groups: history of procedures used for treatment of cardiovascular disease (coronary artery bypass graft, angioplasty, pacemaker or defibrillator implantation, any surgery on the heart or the arteries)
• Active treatment for cancer
• Serious medical condition which could hinder participation or make it unlikely that one will live for three years
• Weight > 300 lbs. (maximum weight allowed on computed tomography [CT] tables)
• Inability to provide an informed consent
• For females, current pregnancy; women wishing to participate may be enrolled six weeks after delivery.
• Contraindications to MRI scanning, (e.g. aneurysm clip, pacemaker, metallic prosthesis, or foreign body)
• Contraindications to gadolinium contrast agent (i.e., history of anaphylaxis)