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）：侵略性脂质修饰对下肢预防动脉粥样硬化和再狭窄进展的益处尚不清楚。缺乏对血管病变病理学的定量测量，严重阻碍了这一领域。手术干预后的完整自然病史尚不清楚。我们将在贝勒医学院的多学科方法中结合我们的专业知识和资源，以解决这些重要问题。我们假设一种积极的血清脂质修饰方案将抑制股动脉动脉粥样硬化的进展，并通过减少血栓形成和炎症后血管内置入后股骨动脉再狭窄的发生率。我们将在一条腿中招募120例有症状性股动脉闭塞性疾病的患者。这些患者将接受血管内置置治疗，并随机分为两组：1）标准医疗保健和2）攻击性脂质改性疗法，可增加HDL（> 40mg/dl），并降低LDL（<80 mg/dl）和TG（Cl50 mg/dl）。我们将关注这些患者2年。我们的具体目的是：1）确定侵袭性脂质修饰对股动脉的动脉粥样硬化和再狭窄的进展的影响。最近，我们改编了高分辨率磁共振成像（MRI），以研究肢体病理学的肢体病变，包括病变大小，组成和形态。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进行动脉粥样硬化的进展或退化。 2）确定血清脂质修饰的侵略性方案对股动脉血管成形术和/或支架后临床适用的血液动力学测量以及对全身性主要心血管事件的减少的影响。贝勒（Baylor）的大量临床体积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，包括脚踝臂指数（ABI），步行距离，绝对闭环和双层超声在具有重要垫垫的人群中。 3）。研究侵袭性三重药物治疗对脂蛋白，炎症以及与垫进展，再狭窄和临床事件的关系的影响。 LDL，HDL，TG，LP（A），粒径和数字的测定，HSCRP，TNFALPHA，IL-8，MCP-1，SP-SELECTIN，S-ICAM-1，S-VCAM-1，S-VCAM-1和SCD40L，将允许机械洞察力介绍到粘贴进展和临床事件中。 4）。研究侵略性三重药物治疗对血栓形成的影响以及与垫进展，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图像的关联将允许对PAD进展和临床事件的机械见解。这项研究将提供一种新的策略，以阻止或预防动脉血运重建程序后动脉粥样硬化和再狭窄的进展。重要的是，我们的MRI研究将首次提供有关血管病变的定量数据。最后，这些研究将提高我们对与侵袭性脂质改性相关的炎症和血栓形成的分子机制的理解。