Vascular Aging: The Link That Bridges Age to Atherosclerosis (The VALIDATE Study)

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. These findings suggest that normal aging alters the vascular substrate so as
to promote the development and progression of atherosclerosis. The age-associated changes in
vascular structure and function include an increase in central vascular stiffness, intimal
proliferation, and endothelial dysfunction. The major hypothesis is that the above
alterations in vascular substrate (i.e. vascular age) are an important determinant of the age
associated increased likelihood for the development and progression of coronary
atherosclerotic disease.

This protocol will non-invasively characterize vascular age and atherosclerotic burden in
BLSA participants and individuals with successful aging, i.e. those with no or minimal
evidence of coronary atherosclerotic disease, and those with premature, clinically evident
coronary artery disease. It will repeat measures of vascular age and atherosclerotic burden
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 two to three-year period,
it will test the hypothesis that vascular age is an important determinant of the
age-associated increase in atherosclerotic disease.

- INCLUSION CRITERIA:

For all groups:

1. Age 30 years or older

2. Ability and willingness to participate in the protocol and undergo vascular studies
and chest MDCT examinations

For the second group:

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

For the third group:

1) Coronary artery calcium score which is greater than the 50th percentile of that computed
based on age and gender, or known coronary disease on the basis of:

i. prior documented myocardial infarction or

ii. typical ischemic symptoms and catheterization documented stenosis of greater than or
equal to 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

1. Atrial fibrillation (due to limitations with gating on MDCT)

2. For the first 2 groups: History of procedures used for treatment of CVD (CABG,
angioplasty, pacemaker or defibrillator implantation, any surgery on the heart or the
arteries)

3. Active treatment for cancer

4. Serious medical condition which could hinder participation or make it unlikely that
they will live for three years (for f/u)

5. Weight>300 lb (maximum weight allowed on CT tables)

6. Inability to provide an informed consent

7. For females, current pregnancy because of the radiation associated with the helical CT
and the unknown risks to a fetus. This is only temporary, and women wishing to
participate may be enrolled six weeks after delivery.