EFFECT OF LIPID MODIFICATION ON PERIPHERAL ARTERIAL DISEASE AFTER ENDOVASCULA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. It is estimated that peripheral arterial disease (PAD), a manifestation of systemic atherosclerosis, occurs in approximately 12% of the adult population and affects about 8 million to 10 million people in the United States. The most common symptomatic manifestation of mild to moderate PAD is intermittent claudication occurring at an annual incidence of 2% in people over 65 years of age. These patients are at a significantly higher risk of death compared with healthy controls of a similar age. However, despite the high prevalence of PAD and its strong association with cardiovascular morbidity and mortality, the disease receives relatively little attention, and PAD patients are less likely to receive appropriate treatment for their atherosclerotic risk factors than those with coronary artery disease. The most common cardiovascular risk factors for coronary artery and PAD include smoking, diabetes, hypertension, dyslipidemia, and abnormalities of homocysteine metabolism. Several large clinical trials have determined the benefits of lowering cholesterol concentrations in patients with coronary artery disease. In PAD, treatment therapy with a statin not only lowers serum cholesterol concentrations, but also improves endothelial function, as well as other markers of atherosclerotic risk, such as serum P-selectin concentrations. Treatment may improve cardiovascular outcomes in persons with peripheral arterial disease. Not only are cardiovascular morbidity and mortality increased with PAD, but functional status is often severely impaired in patients with intermittent claudication. Peak exercise performance in the claudicating patient is about 50% that of age-matched controls, which is equivalent to moderate to severe heart failure using New York Heart Association criteria. The limited ability to ambulate leads to a disability that is particularly detrimental to quality of life because both leisure and work activities are often severely curtailed. This disability can limit normal activities substantially and because improvement in the absence of an intervention is rare, therapy to relieve intermittent claudication is essential. Several therapeutic techniques currently exist for the treatment of PAD in the lower extremities. Surgical revascularization is a viable alternative because the associated risks of periprocedural mortality and morbidity are low, even at an early stage. In addition, PTA (percutaneous angioplasty) procedures have favorable complication and long-term patency rates which have improved with the advent of endovascular stents. The diagnosis of PAD which is reflected in a lowered ankle-brachial blood pressure index (ABI), is highly correlated with the risk of cardiac and cerebrovascular events. This recognition has led to the recommendation that the diagnosis should lead to increased risk modification. Although lowered ankle brachial index is well documented as a marker for cardiovascular morbidity in general, there is less data on the patient who presents with claudication, where intervention is performed for claudication and in whom the lower extremity progression of atherosclerosis is likely to be the ultimate determinant of patency and relief of symptoms. This study will examine the outcomes of risk factor modification in symptomatic PAD patients by evaluating the effects of administering an intensive combination lipid modifying therapy versus a standard lipid modifying therapy in a novel approach to preventing progression of atherosclerosis and restenosis following an endovascular intervention.