Peripheral arterial disease (PAD) is found in almost 20% of the population aged 55 and older. It is responsible for incapacitating symptoms of leg pain when walking, culminating in amputation in a small proportion of patients. Further, the presence of PAD is a strong marker for future cardiovascular events such as myocardial infarction and stroke. Despite the clinical significance of PAD, it is under diagnosed and its pathobiology remains ill defined. While imaging studies play an integral role in the study of most disease processes, angiography, standard ultrasound examination, and even magnetic resonance imaging do not provide adequate resolution of the arterial wall to quantify and characterize the extent of vascular wall abnormalities or to track changes over time. Intravascular ultrasound (IVUS) technology is associated with spatial resolution of 80-100 fm radially and 150-200 fm circumferentially. As such, IVUS appears ideally suited to the quantification of vascular wall changes. Our group has studied IVUS in the characterization of coronary artery plaque morphology, correlating clinical signs and symptoms with atheroma burden and content. We propose similar studies in the peripheral arterial bed, quantifying the amount and composition of lower extremity arterial atheroma and relating these findings to the patients' clinical presentation and subsequent course. This goal will be accomplished through the completion of three separate but concurrent studies: (1) Histologic sections of fresh arterial segments from cadaver limbs and amputation specimens will be correlated with IVUS-derived radiofrequency data to quantify arterial plaque burden and composition (calcium, collagen, fibro-lipidic and necrotic components). (2) Patients undergoing standard lower extremity angiography for PAD will be studied with IVUS at the same sitting. IVUS findings will be correlated with demographic factors (age, gender, race) and symptom severity (claudication, rest pain, tissue loss). Patients will be followed for up to five years, and the occurrence of ischemic events (worsening of leg ischemia, need for intervention and re-intervention, and distant complications such as Mi and stroke) will be reconciled with the arterial wall content at the baseline examination. (3) A randomized, blinded clinical trial of high-dose atorvastatin vs. placebo will be performed in patients with intermittent claudication, based on our hypothesis that statin therapy will result in stabilization or regression of femoral artery plaque, differences best assessed with high resolution imaging studies. IVUS data will be collected at baseline and at 24 months. The primary endpoint will be the change in femoral arterial plaque volume; baseline arterial wall parameters will be assessed in the subgroup of stain responders vs. non-responders. The completion of these three investigations should yield a validated, high resolution, real time imaging study with which to assess risk and base treatment decisions in patients with PAD.
| Arthurs, Zachary M; Bishop, Paul D; Feiten, Lindsay E et al. (2010) Evaluation of peripheral atherosclerosis: a comparative analysis of angiography and intravascular ultrasound imaging. J Vasc Surg 51:933-8; discussion 939 |
| Eagleton, Matthew J; Bishop, Paul D; Bena, James F et al. (2008) Calcium channel blockers and angiotensin-converting enzyme inhibitors may be associated with altered atherosclerotic plaque size and morphology. Vascular 16:171-8 |
| Kashyap, Vikram S; Pavkov, Mircea L; Bishop, Paul D et al. (2008) Angiography underestimates peripheral atherosclerosis: lumenography revisited. J Endovasc Ther 15:117-25 |
| Bishop, Paul D; Feiten, Lindsay E; Ouriel, Kenneth et al. (2008) Arterial calcification increases in distal arteries in patients with peripheral arterial disease. Ann Vasc Surg 22:799-805 |
