Analytical Performance/Clinical Utility Of Lab Tests

实验室测试的分析性能/临床实用性

• 批准号: 7215829
• 负责人: Gyorgy Csako
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7215829
• 关键词: atherosclerosis; cardiovascular disorder diagnosis; colony stimulating factor; diagnosis design /evaluation; high density lipoproteins; human subject; low density lipoprotein; major depression; patient oriented research; thrombosis

Atherothrombosis is a multifactorial disease and risk factors for atherothrombosis are now estimated to be in the hundreds. In addition to classical risk factors like serum lipids (total cholesterol and triglycerides), lipoproteins, apolipoproteins, and a variety of other factors such as infections with corresponding antibodies, autoimmune constituents with corresponding antibodies, inflammatory molecules such as C-reactive protein (CRP), and hemostatic factors have been also considered for risk. In systematic review and meta-analysis of randomized controlled trials, we compared the efficacy and safety of two major natural therapies, plant sterols/stanols and policosanol, in the treatment of coronary heart disease, as measured by alterations in various plasma lipid levels. We searched MEDLINE, EMBASE, the Web of Science, and the Cochrane Library from January 1967-June 2003 to identify pertinent studies. A total of 4596 patients were available for analysis from 52 eligible studies (23 for plant sterols/stanols and 29 for policosanol). Reduction of low-density lipoprotein-cholesterol (LDL-C) levels was the primary end-point; effects on other lipid parameters and withdrawal of study patients due to adverse effects were the secondary end-points. The net LDL reduction in the treatment groups minus that in the placebo groups was greater with policosanol than plant sterols and stanols (-24% versus -10%, p less than 0.0001). Policosanol also affected total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and triglyceride levels more favorably than plant sterols and stanols. Further, policosanol caused a clinically significant decrease in the LDL-C:HDL-C ratio. The withdrawal rate due to adverse effects and combined relative risk for patients who withdrew were 0% and 0.84, respectively (p equal to 0.69), for plant sterols/stanols across 20 studies versus 0.86% and 0.31, respectively (p less than 0.0001), for policosanol across 28 studies. Based on these results, we concluded that plant sterols/stanols and policosanol are well tolerated and safe; however, policosanol is more effective than plant sterol/stanols for LDL-C level reduction and more favorably alters the lipid profile, approaching antilipemic drug efficacy. Over the past year, we also carried out several collaborative studies. In a pilot clinical trial, we studied the outcomes and risks of granulocyte colony-stimulating factor (G-CSF) administration to patients with severe coronary artery disease. Patients with CAD who experience frequent angina despite attempts at revascularization are encountered with increasing frequency. We hypothesized that G-CSF administration to CAD patients may mobilize progenitor cells from bone marrow, without evidence of platelet or thrombosis activation. On the other hand, significant increases in inflammatory cells and CRP would destabilize plaques and cause adverse outcomes during treatment. Although symptoms improved in many patients following administration of G-CSF, we found no evidence of objective cardiac benefit by this cytokine-based therapeutic approach. In another collaborative study, we studied the possible mechanism(s) of increased cardiovascular risk in young premenopausal women with major depressive disorder (MDD). MDD is one of the most common psychiatric illnesses in the adult population and is often associated with an increased risk of cardiovascular disease. Although at the time of evaluation, our study subjects with MDD were mildly depressed and mostly in clinical remission on antidepressants, they had more abdominal fat and increased serum levels of prothrombotic factors (plasminogen activator inhibitor-1 [PAI-1] concentration and coagulation factor VIII [fVIII] activity) than healthy controls. The observed alterations in body fat distribution (increased abdominal fat) and prothrombotic factors (increased PAI-1 and fVIII) may be in part responsible for the increased risk of cardiovascular disease reported in association with major depression.

动脉粥样硬化血栓形成是一种多因素疾病，目前估计动脉粥样硬化血栓形成的危险因素有数百种。除了经典的风险因素如血清脂质（总胆固醇和甘油三酯），脂蛋白，载脂蛋白和各种其他因素如感染相应的抗体，自身免疫成分与相应的抗体，炎症分子如C-反应蛋白（CRP），止血因素也被认为是风险。在随机对照试验的系统回顾和荟萃分析中，我们比较了两种主要的自然疗法，植物甾醇/甾烷醇和多廿烷醇，在治疗冠心病中的有效性和安全性，通过改变各种血脂水平来衡量。我们检索了MEDLINE、EMBASE、Web of Science和科克伦图书馆1967年1月至2003年6月的相关研究。共有4596例患者可用于52项合格研究的分析（23项植物甾醇/甾烷醇和29项多廿烷醇）。降低低密度脂蛋白胆固醇（LDL-C）水平是主要终点;对其他血脂参数的影响和因不良反应而退出研究的患者是次要终点。治疗组中的净LDL降低减去安慰剂组中的净LDL降低，多廿烷醇组大于植物甾醇和甾烷醇组（-24% vs-10%，p <0.0001）。与植物甾醇和甾烷醇相比，多廿烷醇对总胆固醇、高密度脂蛋白胆固醇（HDL-C）和甘油三酯水平的影响更大。此外，多廿烷醇导致LDL-C：HDL-C比值出现具有临床意义的降低。在20项研究中，植物甾醇/甾烷醇因不良反应而退出的患者的退出率和合并相对风险分别为0%和0.84（p = 0.69），而在28项研究中，多廿烷醇分别为0.86%和0.31（p <0.0001）。基于这些结果，我们得出结论，植物甾醇/甾烷醇和多廿烷醇耐受性良好且安全;然而，多廿烷醇比植物甾醇/甾烷醇更有效降低LDL-C水平，更有利地改变脂质谱，接近降脂药物疗效。 在过去一年中，我们还进行了几项合作研究。在一项初步临床试验中，我们研究了粒细胞集落刺激因子（G-CSF）给药于严重冠状动脉疾病患者的结局和风险。尽管尝试了血运重建，但仍频繁发生心绞痛的CAD患者的发生率越来越高。我们假设CAD患者给予G-CSF可能动员骨髓祖细胞，而没有血小板或血栓激活的证据。另一方面，炎症细胞和CRP的显著增加会使斑块不稳定，并在治疗期间引起不良后果。虽然许多患者在给予G-CSF后症状改善，但我们没有发现这种基于精氨酸的治疗方法对心脏有客观益处的证据。在另一项合作研究中，我们研究了患有重度抑郁症（MDD）的年轻绝经前女性心血管风险增加的可能机制。MDD是成年人群中最常见的精神疾病之一，通常与心血管疾病风险增加有关。尽管在评价时，我们的研究中MDD受试者有轻度抑郁，且大多数在抗抑郁药物治疗后处于临床缓解状态，但与健康对照组相比，他们的腹部脂肪更多，血清血栓前因子水平（纤溶酶原激活物抑制剂-1（派-1）浓度和凝血因子VIII（fVIII）活性）升高。观察到的体脂分布（腹部脂肪增加）和促血栓形成因子（派-1和fVIII增加）的变化可能是导致与重度抑郁症相关的心血管疾病风险增加的部分原因。