EFFECT OF LIPID MODIFICATION ON PERIPHERAL ARTERIAL DISEASE AFTER ENDOVASCULA

脂质修饰对血管内术后周围动脉疾病的影响

• 批准号: 7605937
• 负责人: ALAN LUMSDEN
• 金额: $ 2.78万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-15 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605937
• 关键词: Adult; Affect; Age; Age-Years; Angiography; Angioplasty; Ankle; Arteries; Atherosclerosis; Attention; Blood Tests; Cardiovascular system; Caring; Cessation of life; Cholesterol; Cholestyramine; Clinical; Clinical Trials; Clofibrate; Colestipol; Combined Modality Therapy; Complication; Computer Retrieval of Information on Scientific Projects Database; Contralateral; Coronary Arteriosclerosis; Diabetes Mellitus; Diet; Disease; Disease Progression; Disease regression; Dyslipidemias; Event; Exercise; Funding; Grant; Heart; Heart failure; High Density Lipoproteins; High Prevalence; Homocysteine; Homocystine; Hypertension; Image; Imaging technology; Incidence; Inflammation; Institution; Intermittent Claudication; Intervention; Leg; Limb structure; Lipids; Lipoproteins; Low-Density Lipoproteins; Lower Extremity; Magnetic Resonance Imaging; Measurement; Measures; Medical; Meta-Analysis; Metabolism; Modification; Morbidity - disease rate; New York; Nicotinic Acids; Operative Surgical Procedures; Outcome; P-Selectin; Pathology; Patients; Performance; Peripheral arterial disease; Persons; Physiologic pulse; Placebos; Population; Pulse taking; Quality of life; Questionnaires; Randomized; Randomized Controlled Clinical Trials; Rate; Recruitment Activity; Research; Research Personnel; Resolution; Resources; Risk; Risk Factors; Serum; Severities; Smoking; Source; Staging; Standards of Weights and Measures; Stents; Symptoms; Techniques; Therapeutic; Thrombosis; Ultrasonography; United States; United States National Institutes of Health; Walking; Work; cardiovascular risk factor; claudication; disability; ezetimibe; femoral artery; functional status; hemodynamics; improved; men; mortality; pressure; restenosis

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. I. HYPOTHESIS The hypothesis for the study is as follows: Intensive lipid modification with combination therapy will inhibit the progression of atherosclerosis and reduce the incidence of restenosis in femoral arteries following endovascular stenting by decreasing thrombosis and inflammation. II. SPECIFIC AIMS In general, 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 then randomized into two treatment groups: 1). standard of medical care including statin therapy; and 2) standard of medical care with intensive lipid modification using a statin plus ezetimibe and extended release niacin to increase HDL (>40) and decrease LDL (<80) and TG (<150). Specifically, we will follow these patients for 2 years and study the following specific aims: 1. To determine the effect of intensive lipid modification therapy on progression of atherosclerosis and restenosis of femoral arteries using high resolution MRI image technology to exam both the stented femoral artery for in-stent restenosis and the contralateral fermoral artery for progression of atherosclerosis. 2. To determine the effect of intensive lipid modification therapy on the clinically applicable hemodynamic measurements, clinical symptoms, reduction in systemic major cardiovascular events and the general quality of life of patients following PTA revascularization and stenting by assessment with Duplex ultrasound, segmental limb pressure, segmental pulse volume recording, ankle brachial indicies, treadmill walking distance, absolute claudication and quality of life questionnaires. 3. To determine the effect of intensive lipid modification therapy on lipoproteins, inflammation, and relationship to PAD progression, restenosis, and clinical events. 4. To determine the effect of intensive lipid modification therapy on thrombosis, and relationship to PAD progression, restenosis and clinical events. The association of these blood tests with clinical outcome and femoral artery image will be determined. III. BACKGROUND AND SIGNIFICANCE It is estimated that peripheral arterial disease (PAD), a manifestation of systemic atherosclerosis, occurs in approximately 12% of the adult population, affecting about 8 million to 10 million persons in the United States (1, 2). The most common symptomatic manifestation of mild to moderate atherosclerotic PAD is intermittent claudication, which occurs at an annual incidence of 2% in persons over 65 years of age (3). These patients are at a significantly higher risk of death, compared with healthy controls of a similar age (4). However, despite the high prevalence of PAD and its strong association with cardiovascular morbidity and mortality, the disease receives relatively little attention. These patients are less likely to receive appropriate treatment for their atherosclerotic risk factors than are those with coronary artery disease (5, 6). Not only are cardiovascular morbidity and mortality increased in the patient with PAD, but functional status is often severely impaired in those 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 (7,8). 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 (9). This disability can limit normal activities substantially (9) 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) has favorable complication and long-term patency rates and these rates have improved with the advent of endovascular stents. The most common cardiovascular risk factors for CAD and PAD include smoking, diabetes, hypertension, dyslipidemia, and abnormalities of homocysteine metabolism. Treatment of these risk factors may improve cardiovascular outcomes in persons with PAD. Several large clinical trials have determined the benefits of lowering cholesterol concentrations in patients with coronary artery disease (10). In patients with PAD, statin therapy 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 (11, 12). A meta-analysis of randomized trials of lipid-lowering therapy in PAD patients revealed a total mortality of 0.7% in the treated patients, as compared with 2.9% in the patients given placebo, a non-significant difference (13). This analysis demonstrated that lipid-lowering therapy reduces disease progression, as measured by angiography, and the severity of claudication. In the Cholesterol Lowering Atherosclerosis Study, lipid-lowering therapy with colestipol plus niacin was associated with stabilization or regression of femoral atherosclerosis (14). The St. Thomas trial, in which 25 men were treated with diet, cholestyramine, nicotinic acid, or clofibrate for an average of 19 months, demonstrated a beneficial effect of therapy on femoral atherosclerosis (15). However, quantitative measurement of atherosclerosis pathology has not been available for evaluating the effect of lipid therapy. Potential application of intensive lipid modification for PAD has not been studied.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 一、假设 该研究的假设如下：联合治疗的强化调脂将抑制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。 二.具体目标 一般来说，我们将总共招募120名有症状的单腿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，然后随机分为两个治疗组：1)。医疗护理标准，包括他汀类药物治疗； 2) 使用他汀类药物加依折麦布和缓释烟酸的强化调脂医疗护理标准，以增加 HDL (>40) 并降低 LDL (<80) 和 TG (<150)。 具体来说，我们将对这些患者进行两年的跟踪研究，并研究以下具体目标： 1. 采用高分辨率 MRI 图像技术检查支架股动脉是否有支架内再狭窄以及对侧股动脉是否有动脉粥样硬化进展，以确定强化调脂治疗对动脉粥样硬化进展和股动脉再狭窄的影响。 2. 确定强化调脂治疗对临床适用的效果 血流动力学测量、临床症状、全身主要心血管疾病的减少 通过双工超声、节段肢体压力、节段脉搏量评估 PTA 血运重建和支架置入术后患者的事件和总体生活质量 记录、踝臂征象、跑步机步行距离、绝对跛行和 生活质量问卷。 3. 确定强化调脂治疗对脂蛋白、炎症的影响以及与 PAD 进展、再狭窄和临床事件的关系。 4. 确定强化调脂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。 将确定这些血液测试与临床结果和股动脉图像的关联。 三．一、背景及意义 据估计，外周动脉疾病 (PAD) 是全身性动脉粥样硬化的一种表现，大约有 12% 的成年人患有外周动脉疾病 (PAD)，影响着美国约 800 万至 1000 万人 (1, 2)。 轻度至中度动脉粥样硬化性 PAD 最常见的症状表现是间歇性跛行，65 岁以上人群的年发病率为 2% (3)。 与相似年龄的健康对照相比，这些患者的死亡风险明显更高 (4)。 然而，尽管 PAD 患病率很高且与心血管发病率和死亡率密切相关，但该疾病受到的关注相对较少。与冠状动脉疾病患者相比，这些患者的动脉粥样硬化危险因素不太可能接受适当的治疗 (5, 6)。 PAD 患者的心血管发病率和死亡率不仅增加，而且间歇性跛行患者的功能状态往往严重受损。 跛行患者的峰值运动表现约为年龄匹配对照的 50%，相当于纽约心脏协会标准中的中度至重度心力衰竭 (7,8)。 行走能力有限会导致残疾，这对生活质量尤其不利，因为休闲和工作活动往往受到严重限制 (9)。 这种残疾会严重限制正常活动 (9)，并且由于在没有干预的情况下改善的情况很少见，因此缓解间歇性跛行的治疗至关重要。 目前存在多种治疗下肢 PAD 的治疗技术。 手术血运重建是一种可行的替代方案，因为即使在早期阶段，围手术期死亡率和发病率的相关风险也很低。 此外，PTA（经皮血管成形术）具有良好的并发症和长期通畅率，并且随着血管内支架的出现，这些通畅率有所提高。 CAD 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。治疗这些危险因素可能会改善 PAD 患者的心血管结局。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 (10)。对于 PAD 患者，他汀类药物治疗不仅可以降低血清胆固醇浓度，还可以改善内皮功能以及动脉粥样硬化风险的其他标志物，例如血清 P-选择素浓度 (11, 12)。对 PAD 患者降脂治疗随机试验的荟萃分析显示，接受治疗的患者的总死亡率为 0.7%，而接受安慰剂的患者的总死亡率为 2.9%，差异不显着 (13)。该分析表明，降脂治疗可减少血管造影测量的疾病进展以及跛行的严重程度。在降低胆固醇动脉粥样硬化研究中，考来替泊加烟酸降脂治疗与股动脉粥样硬化的稳定或消退相关 (14)。圣托马斯试验对 25 名男性进行了平均 19 个月的饮食、考来烯胺、烟酸或安妥明治疗，结果证明该疗法对股动脉粥样硬化具有有益效果 (15)。然而，动脉粥样硬化病理学的定量测量尚未可用于评估脂质治疗的效果。尚未研究强化脂质修饰在 PAD 中的潜在应用。