EFFECT OF LIPID MODIFICATION ON PERIPHERAL ARTERIAL DISEASE AFTER ENDOVASCULA

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。据估计，外周动脉疾病（PAD），一种全身性动脉粥样硬化的表现，发生在大约12%的成年人群中，在美国影响大约800万至1000万人。轻度至中度PAD最常见的症状表现是间歇性跛行，在65岁以上人群中的年发病率为2%。这些患者的死亡风险明显高于同龄的健康对照组。然而，尽管PAD的高患病率及其与心血管发病率和死亡率的强相关性，但该疾病受到的关注相对较少，并且PAD患者与冠状动脉疾病患者相比，其动脉粥样硬化风险因素接受适当治疗的可能性较小。冠状动脉和PAD最常见的心血管危险因素包括吸烟、糖尿病、高血压、血脂异常和同型半胱氨酸代谢异常。几项大型临床试验已经确定了降低冠状动脉疾病患者胆固醇浓度的益处。在PAD中，用他汀类药物治疗不仅降低血清胆固醇浓度，而且改善内皮功能，以及动脉粥样硬化风险的其他标志物，如血清P-选择素浓度。治疗可以改善外周动脉疾病患者的心血管结局。PAD不仅会增加心血管疾病的发病率和死亡率，而且间歇性跛行患者的功能状态通常会严重受损。跛行患者的峰值运动能力约为年龄匹配对照组的50%，相当于使用纽约心脏协会标准的中度至重度心力衰竭。行走能力有限导致残疾，这对生活质量特别有害，因为休闲和工作活动往往受到严重限制。这种残疾可以大大限制正常活动，因为在没有干预的情况下改善是罕见的，治疗以缓解间歇性跛行是必不可少的。目前存在用于治疗下肢PAD的几种治疗技术。手术血运重建是一种可行的替代方案，因为围手术期死亡率和发病率的相关风险较低，即使在早期阶段也是如此。此外，PTA（经皮血管成形术）手术具有良好的并发症和长期通畅率，随着血管内支架的出现，这一点得到了改善。PAD的诊断反映在踝臂血压指数（ABI）降低，与心脏和脑血管事件的风险高度相关。这一认识导致了诊断应导致增加风险修改的建议。虽然踝臂指数降低一般被认为是心血管疾病发病率的标志，但关于跛行患者的数据较少，对跛行进行干预，下肢动脉粥样硬化进展可能是通畅和症状缓解的最终决定因素。本研究将通过评价强化联合调脂治疗与标准调脂治疗在预防血管内介入治疗后动脉粥样硬化和再狭窄进展的新方法中的效果，检查症状性PAD患者中风险因素调整的结局。

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.