Novel Cardiovascular Risk Factors in Renal Insufficiency

描述(由申请人提供)：即使在调整了年龄、糖尿病、性别和种族因素后，终末期肾病患者的心血管疾病(CVD)发病率仍比普通人群高10-20倍。国家肾脏基金会心血管疾病特别工作组的结论是，应重视与尿毒症相关的危险因素，如蛋白尿、Lp(A)和同型半胱氨酸升高，这些因素的不良反应随着慢性肾脏疾病(CKD)的进展而恶化。由于一半的心血管事件发生在没有任何已知传统危险因素的患者中，因此筛查亚临床心血管疾病以努力识别高危个体是很重要的。CKD患者是否存在心血管疾病，特别是冠状动脉疾病的最佳评估尚不清楚。超声测量颈动脉内膜中层厚度(IMT)已被证明可以评估动脉粥样硬化的程度和严重程度。这项拟议的研究将前瞻性地检查100名无症状的CKD和非糖尿病患者，并确定非传统风险因素，如同型半胱氨酸、脂蛋白(A)和C反应蛋白，是否是亚临床心血管疾病的存在和发展的独立风险因素，这是通过重复测量颈动脉IMT来调整已知心血管风险因素在24个月期间进行的。我们建议利用这种有前景的非侵入性新技术来定量评估亚临床脑血管病。我们正在响应PA-01-127项目公告，其中包括使用流行病学和生化方法来确定CKD患者心血管疾病的新的非传统危险因素的目标。对于基线颈动脉IMT的测定，分析工具将是多元线性回归。变化将通过IMT测量的差异来衡量。使用标准混合效应增长曲线的模型将用于估计个别受试者的斜率和截距，并用于比较由基线或时变协变量定义的群体。阐明这些关系是确定心血管疾病进展的可改变的危险因素的重要组成部分，并可能导致对易于识别的高危人群进行有针对性的医疗干预，以减少疾病的进展。

DESCRIPTION (provided by applicant): The incidence of cardiovascular disease (CVD) is 10-20 fold greater in end-stage renal patients compared to the general population even after adjusting for age, diabetes, gender and race. The National Kidney Foundation Task Force on Cardiovascular Disease concluded that emphasis should be placed on risk factors related to uremia such as proteinuria, elevated Lp(a) and homocysteine whose adverse profile worsens as the chronic kidney disease (CKD) progresses. Because half of all cardiovascular events occur in patients without any known traditional risk factors, it is important to screen for subclinical CVD in an effort to identify high-risk individuals. The optimal evaluation for the presence of cardiovascular disease in particular coronary artery disease in patients with CKD is unknown. Carotid intima-media thickness (IMT) measured by ultrasound has been shown to assess the extent and severity of atherosclerosis. The proposed study will examine prospectively 100 asymptomatic patients with CKD and without diabetes and determine if nontraditional risk factors such as homocysteine, lipoprotein (a) and C-reactive protein are independent risk factor for presence and progression of subclinical cardiovascular disease as measured by repeated noninvasive carotid US measures of IMT adjusting for known cardiovascular risk factors over a 24-month interval. We propose to utilize this promising new non-invasive technique for the quantitative assessment of subclinical CVD. We are responding to program announcement PA-01-127 which includes the objective of use of epidemiological and biochemical approaches to identifying new, non-traditional risk factors for cardiovascular disease in patients with CKD. For the determination of baseline carotid IMT, the tool of analysis will be multiple linear regression. A change will be measured by the difference in IMT measurements. Models using standard mixed effects growth curves will be used to allow both the estimation of individual subjects' slopes and intercepts and for the comparison of groups defined by baseline or time varying covariates. Elucidation of these relationships is an essential component of identifying modifiable risk factors for the progression of cardiovascular disease and may lead to targeted medical interventions to easily identifiable high-risk groups to decrease disease progression.