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: 7950685
• 负责人: CHRISTIE Mitchell BALLANTYNE
• 金额: $ 4万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950685
• 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 Research; 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; 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; Quality of life; Questionnaires; Randomized; Randomized Controlled Clinical Trials; Recruitment Activity; Research; Research Personnel; Resolution; Resources; Risk; Risk Factors; Serum; Severities; Smoking; Source; Staging; 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; high risk; 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. 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. 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: standard of medical care including statin therapy; and standard of medical care with intensive lipid modification using a statin plus ezetimibe and extended release niacin to increase HDL and decrease LDL and TG . 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. 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该研究的假设如下：结合疗法的密集脂质修饰将抑制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于血管内置入后股动脉的再狭窄发生率。 通常，我们将在一条腿中招募120例股骨动脉闭塞性疾病的患者。 这些患者将接受血管内支架的治疗，然后随机分为两个治疗组：包括他汀类药物治疗在内的医疗标准；以及使用他汀类药物加依泽替伯和扩展烟酸的密集脂质修饰的医疗保健标准，以增加HDL并降低LDL和TG。 具体来说，我们将关注这些患者2年，并研究以下具体目标： 1。使用高分辨率MRI图像技术来确定强化脂质修饰疗法对股动脉的动脉粥样硬化和股动脉再狭窄的影响，以检查股骨支架动脉的内部再狭窄和对侧效费疗法动脉，用于动脉粥样硬化的进展。 2。确定强化脂质修饰疗法对临床适用的血液动力学测量，临床症状，减少，全身主要心血管事件的减少以及PTA血运重建后患者的一般生活质量，并通过用二线超声进行评估和置于pTA的置于pta脉冲，分段的cl脉冲，分段脉冲，分段脉冲，分段脉冲，弯曲指示度，弯管，弯管，弯管，弯管，弯管，弯管，弯管，弯管，弯管，弯管，弯管，弯管，锻炼，弯管，弯管，弯曲， 生活质量问卷。 3。确定密集脂质修饰疗法对脂蛋白，炎症以及与垫进展，再狭窄和临床事件的关系的影响。 4。确定密集脂质修饰疗法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。 这些血液检查与临床结果和股动脉图像的关联将得到确定。 背景和意义 据估计，周围动脉疾病（PAD）是全身性动脉粥样硬化的表现，发生在大约12％的成年人口中，影响了美国约800万至1000万人（1，2）。 轻度至中度动脉粥样硬化垫的最常见症状表现是间歇性lau不平，在65岁以上的患者中，每年发生2％的发病率（3）。 与年龄相似的健康对照相比，这些患者的死亡风险明显更高（4）。 然而，尽管PAD的患病率很高及其与心血管发病率和死亡率的密切相关，但该疾病的关注却很少。与冠状动脉疾病的患者相比，这些患者不太可能接受动脉粥样硬化危险因素（5,6）。 患者使用PAD的患者不仅会增加心血管发病率和死亡率，而且在间歇性lauraurauration的患者中，功能状况通常会严重受损。 laudi态患者的峰值运动表现约为年龄匹配的对照的50％，这相当于使用纽约心脏协会标准中度至重度心力衰竭（7,8）。 有限的行动能力会导致残疾特别有害的生活质量，因为休闲和工作活动通常会严重限制（9）。 这种残疾可以大大限制正常活动（9），并且由于在没有干预的情况下进行改善是罕见的，因此可以缓解间歇性lauraurauring的治疗是必不可少的。 目前存在几种治疗下肢治疗PAD的治疗技术。 手术血运重建是一种可行的替代方法，因为即使在早期阶段，围围骨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）具有有利的并发症和长期通畅率，随着血管内支架的出现，这些速率得到了提高。 CAD和PAD的最常见心血管危险因素包括吸烟，糖尿病，高血压，血脂异常以及同型半胱氨酸代谢的异常。这些危险因素的治疗可能会改善PAD患者的心血管结局。几项大型临床试验确定了降低冠状动脉疾病患者胆固醇浓度的好处（10）。在患有PAD的患者中，他汀类药物疗法不仅降低了血清胆固醇浓度，还可以改善内皮功能以及其他动脉粥样硬化风险的标志物，例如血清P-链霉素浓度（11,12）。对PAD患者脂质降低疗法的随机试验的荟萃分析显示，治疗患者的总死亡率为0.7％，而给予安慰剂的患者为2.9％，这是无明显的差异（13）。该分析表明，通过血管造影和laud缩的严重程度，降低脂质疗法可以降低疾病进展。在降低动脉粥样硬化研究的胆固醇中，降低脂质疗法的Colestipol Plus烟酸与股动脉粥样硬化的稳定或消退有关（14）。圣托马斯试验，其中25名男性接受了饮食，胆碱氨酸，烟酸或粘液纤维的平均治疗19个月，这表明治疗对股动脉粥样硬化的有益作用（15）。但是，尚未用于评估脂质疗法的作用的动脉粥样硬化病理学的定量测量。尚未研究强化脂质修饰的潜在应用。