Effect of lipid modification on peripheral arterial dis*

脂质修饰对外周动脉疾病的影响*

• 批准号: 6951747
• 负责人: ALAN B. LUMSDEN
• 金额: $ 2.6万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-22 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6951747
• 关键词: aerobic exercise; angiocardioultrasonography; antihypercholesterolemic agent; artery occlusion; atherosclerosis; blood lipoprotein; blood lipoprotein metabolism; blood tests; blood vessel prosthesis; cardiovascular disorder chemotherapy; cardiovascular disorder prevention; claudication; clinical research; clinical trials; combination chemotherapy; human subject; human therapy evaluation; inflammation; intraluminal angioplasty; longitudinal human study; magnetic resonance imaging; patient oriented research; peripheral blood vessel disorder; restenosis; thrombosis; transforming growth factors

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.

描述（由申请人提供）：积极的脂质修饰对于预防下肢动脉粥样硬化和再狭窄的进展的益处尚不清楚。由于缺乏血管病变病理学的定量测量，该领域受到严重阻碍。手术干预后再狭窄的完整自然史尚不清楚。我们将通过多学科方法结合贝勒医学院的专业知识和资源来解决这些重要问题。我们假设积极的血脂调节方案将抑制股动脉粥样硬化的进展，并通过减少血栓形成和炎症来降低血管内支架置入术后股动脉再狭窄的发生率。我们将总共招募 120 名单腿有症状的股动脉闭塞性疾病患者。这些患者将接受血管内支架置入术治疗，并随机分为两组：1) 标准医疗护理和 2) 积极的调脂疗法，即增加 HDL (>40mg/dl) 并降低 LDL (<80 mg/dl) 和 TG (cl50)。毫克/分升）。我们将对这些患者进行两年的跟踪。我们的具体目标是： 1) 确定积极的脂质修饰对动脉粥样硬化进展和股动脉再狭窄的影响。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学，包括病变大小、成分和形态。该技术将用于检查支架股动脉的支架内再狭窄和对侧股动脉的动脉粥样硬化进展或消退。 2) 确定积极的血脂调节方案对股动脉血管成形术和/或支架置入术后临床适用的血流动力学测量以及对减少全身主要心血管事件的影响。贝勒大学庞大的临床量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，包括患有显着 PAD 的人群的踝肱指数 (ABI)、步行距离、绝对跛行和双功能超声。 3）。研究积极的三药疗法对脂蛋白、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、TNFα、IL-8、MCP-1、sP-选择素、s-ICAM-1、s-VCAM-1 和 sCD40L 的测定将允许对 PAD 进展和临床事件的机制见解。 4).研究积极的三药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。这些研究与临床结果和定量股骨 MR 图像的关联将有助于深入了解 PAD 进展和临床事件。这项研究将为延缓或预防动脉血运重建手术后动脉粥样硬化和再狭窄的进展提供新的策略。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，这些研究将增进我们对与积极脂质修饰相关的炎症和血栓形成的分子机制的理解。