Coronary calcification in hemodialysis patients

描述（由申请人提供）：慢性肾脏疾病（CKD）患者的死亡率增加，心血管疾病（CVD）约占这些患者死亡的50%。这是一种非典型形式的动脉粥样硬化，动脉粥样硬化斑块中钙沉积增加，中膜增厚，传统的危险因素不能完全解释。血管钙化（VC）可能是导致动脉僵硬和左心室肥厚的主要原因。最近的证据表明，慢性炎症状态和骨矿物质代谢和循环VC抑制剂的改变，这是常见的透析患者可能在血管钙化过程中发挥重要作用。我们正在响应PA-06-148与肾脏相关的试点和可行性计划，其目的是使用流行病学和生化方法来确定CKD患者中CVD的新的非传统风险因素。冠状动脉钙化（CAC）在这一人群中很常见，并与死亡率增加有关。脉搏波速度也被发现是独立相关的死亡率在这类患者。这两种非侵入性测量将能够评估每例受试者的血管钙化程度和顺应性。我们假设，在炎症和骨代谢改变水平最高的个体中，CAC将在12个月内比炎症状态和骨代谢正常的个体更普遍，进展更快。我们计划招募125例无症状透析患者，并前瞻性测量CAC和PWV。我们的主要分析工具将是Wilcoxon秩和检验和标准混合效应生长曲线模型。研究结果将有助于确定风险因素，我们可以在未来的随机临床试验中改变其风险特征。此外，它将提供关于当前临床治疗是否增加我们透析人群钙化负担的见解。

DESCRIPTION (provided by applicant): Patients with chronic kidney disease (CKD) have an increased mortality rate and cardiovascular disease (CVD) accounts for approximately 50% of deaths in these patients. It is an atypical form of atherosclerosis with increased deposition of calcium in the atherosclerotic plaque, thickening of the media and not fully explained by traditional risk factors. Vascular calcification (VC) which leads to arterial stiffness and left ventricular hypertrophy is likely to be a major contributant to the pathology. Recent evidence suggest that a chronic inflammatory state and alterations of bone mineral metabolism and circulating VC inhibitors which are common in dialysis patients may play an important role in the vascular calcification process. We are responding to PA-06-148 Pilot and Feasibility Program Related to the Kidney whose objective is to use epidemiological and biochemical approaches to identify new, non-traditional risk factors for CVD in patients with CKD. Coronary artery calcification (CAC) is common in this population and has been associated with increased mortality. Pulse wave velocity has also been found to be independently associated with mortality in this patients. These two non-invasive measurements will be able to provide an assessment of the degree of vascular calcification and compliance in each subject. We hypothesize that in individuals with the highest levels of inflammatory and alteration of bone metabolism, CAC will be more prevalent and progress more rapidly in a 12-month period than in those with normal inflammatory state and bone metabolism. We propose to enroll a cohort of 125 incident asymptomatic dialysis patients and obtain measurements of CAC and PWV prospectively. Our main tool for analysis will be Wilcoxon rank-sum test and standard mixed effects growth curve models. The study findings will aid in identifying risk factors whose risk profile we can alter in future randomized clinical trials. In addition, it will provide insight on whether current clinical therapies are increasing the burden of calcification in our dialysis population.