Effect of lipid modification on peripheral arterial dis*

描述（由申请人提供）：积极的脂质修饰对预防下肢动脉粥样硬化和再狭窄进展的益处尚不清楚。由于缺乏血管病变病理的定量测量，这一领域受到严重阻碍。手术后再狭窄的完整自然病史尚不清楚。我们将结合贝勒医学院的专业知识和资源，采用多学科方法来解决这些重要问题。我们假设积极的血脂修饰方案将通过减少血栓和炎症来抑制股动脉粥样硬化的进展，并减少血管内支架植入术后股动脉再狭窄的发生率。我们将招募120例单腿症状性股动脉闭塞性疾病患者。这些患者将接受血管内支架植入治疗，并随机分为两组：1)标准医疗护理和2)积极的脂质修饰治疗，增加HDL (40mg/dl)，降低LDL （< 80mg /dl）和TG （cl50 mg/dl）。我们将对这些患者进行为期2年的随访。我们的具体目的是：1)确定积极的脂质修饰对动脉粥样硬化和股动脉再狭窄进展的影响。最近，我们采用高分辨率磁共振成像（MRI）来研究四肢血管病理，包括病变的大小、组成和形态。该技术将用于检查支架内股动脉再狭窄和对侧股动脉动脉粥样硬化进展或消退。2)确定积极的血脂修饰方案对股动脉血管成形术和/或支架植入术后临床适用的血流动力学测量的影响，以及对减少全身性主要心血管事件的影响。Baylor的大量临床研究和出色的血管内治疗专业知识将使我们能够评估临床结果，包括踝关节肱指数（ABI）、步行距离、绝对跛行和双相超声。3)。研究积极的三联药物治疗对脂蛋白、炎症的影响，以及与PAD进展、再狭窄和临床事件的关系。LDL、HDL、TG、Lp(a)、颗粒大小和数量、hsCRP、TNFalpha、IL-8、MCP-1、sp -选择素、s-ICAM-1、s-VCAM-1和sCD40L的检测将有助于了解PAD进展和临床事件的机制。4)。探讨积极的三联药物治疗对血栓形成的影响，以及与PAD进展、再狭窄和临床事件的关系。将这些研究与临床结果和定量股骨MR图像相关联，将有助于深入了解PAD进展和临床事件的机制。本研究将提供一种新的策略来延缓或预防动脉血管重建术后动脉粥样硬化和再狭窄的进展。重要的是，我们的MRI研究将首次提供血管病变的定量数据。最后，这些研究将促进我们对与侵袭性脂质修饰相关的炎症和血栓形成的分子机制的理解。

DESCRIPTION (provided by applicant): The benefit of aggressive lipid modification on the prevention of progression of atherosclerosis and restenosis in the lower extremity is unknown. This field is severely hampered by the lack of quantitative measurement of vascular lesion pathology. Complete natural history of restenosis following surgical intervention is not clear. We will combine our expertise and resources at Baylor College of Medicine in a multidisciplinary approach to address these important questions. We hypothesize that an aggressive regimen of serum lipid modification will inhibit the progression of atherosclerosis in femoral arteries and reduce the incidence of restenosis of femoral arteries following endovascular stenting by decreasing thrombosis and inflammation. We will recruit a total of 120 patients with symptomatic femoral artery occlusive disease in one leg. These patients will be treated with endovascular stenting, and randomized into two groups: 1) standard medical care and 2) aggressive lipid modification therapy which increases HDL (>40mg/dl) and decreases LDL (<80 mg/dl) and TG (cl50 mg/dl). We will follow these patients for 2 years. Our Specific Aims are to: 1) Determine the effect of aggressive lipid modification on progression of atherosclerosis and restenosis of femoral arteries. Recently, we have adapted high resolution magnetic resonance imaging (MRI) to study extremity vascular pathology including lesion size, composition, and morphology. This technology will be used to examine both the stented femoral artery for in-stent restenosis and the contralateral femoral artery for atherosclerosis progression or regression. 2) Determine the effects of an aggressive regimen of serum lipid modification on the clinically applicable hemodynamic measurements following femoral artery angioplasty and/or stenting and on the reduction of systemic major cardiovascular events. Large clinical volume and excellent endovascular therapy expertise at Baylor will enable us to evaluate the clinical outcomes, including ankle brachial index (ABI), walking distance, absolute claudication, and duplex ultrasound in a population with significant PAD. 3). Investigate effects of aggressive triple-drug therapy on lipoproteins, inflammation, and relationship to PAD progression, restenosis, and clinical events. Assays of LDL, HDL, TG, Lp(a), particle size and number, hsCRP, TNFalpha, IL-8, MCP-1, sP-selectin, s-ICAM-1, s-VCAM-1, and sCD40L will permit mechanistic insights into PAD progression and clinical events. 4). Investigate the effects of aggressive triple-drug therapy on thrombosis, and relationship to PAD progression, restenosis and clinical events. Association of these studies with clinical outcomes and quantitative femoral MR images will permit mechanistic insights into PAD progression and clinical events. This study will provide a novel strategy to retarding or preventing progression of atherosclerosis and restenosis following arterial revascularization procedures. Importantly, our MRI studies will, for the first time, provide quantitative data on the vascular lesions. Finally, these studies will advance our understanding of the molecular mechanisms of inflammation and thrombosis associated with aggressive lipid modification.